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16 June 2015 Medical laser application: translation into the clinics
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Medical laser applications based on widespread research and development is a very dynamic and increasingly popular field from an ecological as well as an economic point of view. Conferences and personal communication are necessary to identify specific requests and potential unmet needs in this multi- and interdisciplinary discipline. Precise gathering of all information on innovative, new, or renewed techniques is necessary to design medical devices for introduction into clinical applications and finally to become established for routine treatment or diagnosis. Five examples of successfully addressed clinical requests are described to show the long-term endurance in developing light-based innovative clinical concepts and devices. Starting from laboratory medicine, a noninvasive approach to detect signals related to iron deficiency is shown. Based upon photosensitization, fluorescence-guided resection had been discovered, opening the door for photodynamic approaches for the treatment of brain cancer. Thermal laser application in the nasal cavity obtained clinical acceptance by the introduction of new laser wavelengths in clinical consciousness. Varicose veins can be treated by innovative endoluminal treatment methods, thus reducing side effects and saving time. Techniques and developments are presented with potential for diagnosis and treatment to improve the clinical situation for the benefit of the patient.



Medical laser application is a broad area armed with advanced technologies to meet challenges in clinical diagnostics and therapy and to address health care issues that impact broad populations. Recent research and emerging developments provide the vision of improving clinical therapeutic procedures or extending the use of lasers to new fields of medicine. Novel biomedical laser applications and new types of lasers widen the possible spectrum of laser-tissue interactions to improve target-oriented, precise application of laser radiation in clinical practice.

New laser light application techniques as well as innovative medical keyhole techniques are under development or at the translational stage in clinics. Highly sophisticated targeting strategies, including endogenous or applied fluorophores, conjugates of nanoparticles, and antibodies, pave the way for new treatment modalities. Combination therapies such as the synergetic use of photodynamic therapy (PDT) and immune-modulatory agents or antiseptics are new fields for research and clinical studies. Improved understanding of biological reactions triggered by laser radiation interacting with natural absorbing sites, targeting molecules, photosensitizers, or nanoparticles will lead to progress in the creation of minimally invasive clinical laser light applications, or assist in elucidating particular immunological responses of the tissue. Theoretical considerations and modeling of laser light distribution in tissue with subsequent energy transfer and tissue interactions constitute a solid basis for therapy planning in patients, particularly if combined with improved light delivery and monitoring techniques.

“Medical Laser Applications and Laser-Tissue Interactions” is a subconference during the European Conference on Biomedical Optics held biannually in Munich. Presentations from around the world covering all fields of laser applications in medicine are regularly presented. This conference provides an interdisciplinary forum for scientists, engineers, technicians, and medical doctors using laser-assisted treatment modalities to discuss progress in all these topics. This forum supports presentations ranging from in vitro investigations to clinical studies of new laser light irradiation modalities in the range of 103 to 1018Wcm2, which can eventually lead to the development of new laser-assisted techniques that can play an important role in the future.

Laser light applications in medicine are based on effects ranging from thermal to nonthermal laser-tissue interactions, which includes ionization effects either on the macro-scale (e.g., in the case of soft tissue smoothing without ablation), on the micro-scale (e.g., in the case of selective retina therapy), or on the nano-scale (e.g., in the case of surgery within cells), as well as short-pulsed laser applications. Generally, both soft and hard tissues can be treated.

There are a variety of medical societies, e.g., ophthalmology, dermatology, and urology, where laser-assisted applications are already part of routine diagnostics and therapy. Here, advancing laser medical applications are summarized, which are close to entering into clinical practice, e.g., noninvasive detection of iron deficiency, improvements in the treatment of glioblastoma multiforme (GBM), photonic technologies for breast cancer (BC) management ranging from risk assessment to therapy, minimally invasive endonasal surgery, and endoluminal laser treatment of varicose veins. It is intended to describe the way how unsolved or insufficiently solved problems in clinical medicine can be overcome step-by-step by suitable technical solutions, which requires identifying the white spots as well as bridging the gap between the research bench and bedside.


Detection of Iron Deficiency

In the following, we will report about previously published studies.1,2 Iron deficiency is a worldwide form of malnutrition, which increases the risk of disability and death. In particular, infants, young children, adolescents, menstruating, and pregnant women often suffer from iron deficiency, which causes anemia and other adverse effects, including impaired cognitive development, decreased immune responsiveness, and, when severe, increased mortality.3 Iron supplementation and food iron fortification are methods to prevent or correct nutritional iron deficiency.3 In the absence of malaria, universal iron supplementation did not affect mortality,4 but in a malarial area, it increased the risk of severe illness and death in iron-replete children.3,5,6 For this reason, the World Health Organization concluded that universal iron supplementation should not be implemented without screening for iron deficiency.6


Diagnostic Problem

Iron deficiency can be detected by several methods,711 which are invasive and require tissue or blood samples for laboratory analysis. Zinc protoporphyrin-IX (ZnPP), a metallo-porphyrin, is produced during heme biosynthesis when the supply of iron is limited and, therefore, is alternatively formed instead of heme by ferrochelatase (EC from zinc ions and protoporphyrin-IX (PPIX), yet in a very low concentration, as shown in Fig. 1. Both, ZnPP and PPIX are located within erythrocytes.12. For diagnostic purposes, the ZnPP/heme ratio is preferred over the absolute concentration of ZnPP (Ref. 12) as the ratio is independent of patient hematocrit. An elevated ZnPP/heme ratio most commonly indicates iron deficiency or lead exposure,1114 and a lowered ZnPP/heme ratio may be found in hereditary hemochromatosis.12,15 The upper threshold for the ZnPP/heme ratio differs between studies and methods but is usually in the range of 40 to 80μmol ZnPP/mol heme.7,12,16 Especially in hospitalized patients, the specificity of the ZnPP/heme ratio for nutritional iron deficiency may be influenced by coexisting disorders, such as lead poisoning, anemia of chronic disease, or chronic inflammation.7,17,18 In some circumstances, the ZnPP/heme ratio may serve as an index of chronic inflammation and can be used to monitor the effectiveness of treatment.17

Fig. 1

Synthesis of zinc protoporphyrin-IX (ZnPP) instead of heme in case of Fe deficiency.12


Routinely, ZnPP and PPIX concentrations can be measured by extraction and high-performance liquid chromatography (HPLC) separation13,19 and detection by its fluorescence light emission upon blue light excitation. To calculate the ZnPP/heme ratio, additionally a routine Hb measurement is required. A low-cost and rapid method for determining the ZnPP/heme ratio is the use of a portable front-face fluorometer, the hematofluorometer,20 requiring only a drop of (capillary or venous) blood, which directly measures the fluorescence light emitted by the erythrocyte ZnPP. In reasonable approximation, the signal is independent of the hematocrit20 and is a direct measure for the ZnPP/heme ratio.20,21 Due to its simplicity, the hematofluorometer is recommended as a screening device for targeted iron supplementation.22 However, the signal detected is influenced by background fluorescence of other blood constituents.16,2327 Potential elimination of background fluorescence entails further requirements, e.g., extended sample preparation time, additional laboratory equipment, and trained personnel. The application of this device is thus restricted if cost-effective measurements are needed, laboratory infrastructure is not available, or venipuncture is not feasible, e.g., in the case of point-of-care screening for iron deficiency under field conditions.22


Noninvasive Method

A method to measure the ZnPP/heme ratio independent of wthe background fluorescence is the dual-wavelength excitation method. This technique eliminates the autofluorescence background while retaining the porphyrin fluorescence emission.1,2,28 Employing two laser diodes at 407 and 425 nm, it shows potential for field diagnosis while removing the need to wash the erythrocytes prior to ZnPP/heme ratio determination. In Fig. 2, the background-free ZnPP fluorescence signal measured from diluted whole blood is correlated with a reference HPLC measurement.

Fig. 2

Correlation of background-free ZnPP fluorescence (y axis) to standard evaluation using high-performance liquid chromatography (x axis).1


In further investigations, the dual-wavelength excitation method1 will be applied to noninvasive autofluorescence measurements to measure the faint erythrocyte ZnPP fluorescence noninvasively. The oral mucosa has been identified as a potential site to conduct these measurements, because the blood vessels are covered only by a thin, nonpigmented epithelial layer, such that light penetration of excitation light is not hindered. The capillary blood density is high, so that a sufficient amount of ZnPP fluorophores can be expected in the illuminated tissue volume. Still, background fluorescence is expected to be an even greater problem than for the whole-blood measurements. Among the main tissue fluorophores are collagen and elastin crosslinks,29 whose fluorescence intensities are assumed to considerably exceed the ZnPP fluorescence signal remitted from tissue surfaces. Therefore, a method to efficiently reduce tissue background fluorescence also would be needed for successful noninvasive ZnPP/heme ratio quantitation. It was shown that the dual-wavelength excitation method eliminated, on average, 92% of the autofluorescence background for 20 subjects.2

In conclusion, these studies showed that the dual-wavelength excitation method successfully eliminates the autofluorescence background in whole blood while retaining the porphyrin fluorescence emission. Therefore, this approach allows for the construction of a simple, inexpensive point-of-care instrument quantifying the ZnPP/heme ratio from unwashed whole blood. For a future point-of-care instrument that quantifies the ZnPP/heme ratio noninvasively from the oral mucosa, dual-wavelength excitation can be used to largely eliminate the overwhelming tissue autofluorescence background to permit the quantitation of the faint ZnPP fluorescence signal.


Treatment of Glioblastoma Multiforme in Neurosurgery

GBM ranks among the oncological diseases with the worst prognosis. At an incidence rate of 3 to 4 per 100,000 people,30 the median survival after initial diagnosis is age-dependent and ranges from 6 to 9 months for older patients to 18 to 21 months for younger patients.31 GBM is a devastating disease, despite improvements in survival rates achieved so far, and there is an urgent need for innovative treatment concepts. Survival after surgery and radiotherapy of malignant gliomas is linked to the completeness of tumor removal.3234 Therefore, methods that permit intraoperative identification of residual tumor tissue may be beneficial. The aim of initial open surgery is to remove most of the tumor volume as indicated by preoperative magnetic resonance imaging (MRI) with contrast agent. There is increasing evidence that “safe gross total resection” is correlated with improved recurrence free survival.35


Fluorescence-Guided Resection

Several malignant tissues synthesize increased amounts of endogenous porphyrins after exposure to 5-aminolevulinic acid (5-ALA). It has been shown that C6 glioma cells, as a model for human malignant glioma, similarly synthesize porphyrins when exposed to 5-ALA and that selective synthesis occurs when C6 cells are inoculated into rat brains to form a tumor.36 The kinetics of porphyrin fluorescence intensities in cultured C6 cells was investigated by flow cytometry. According to these in vitro and in vivo experiments, after exposure to 5-ALA, cultured C6 cells show a linear increase of PPIX fluorescence, which begins to plateau after 85 min. Marked fluorescence is also observed in solid and infiltrating experimental tumor. However, faint fluorescence also occurs in normal tissue. Based on these encouraging investigations, first, clinical applications could be envisioned, and subsequently, the benefit of fluorescent porphyrins that accumulate in malignant tissue after administration of a precursor (5-ALA) for labeling of malignant gliomas in patients could be confirmed.37 For doing this intraoperatively, available clinical techniques and equipment from urological fluorescence diagnosis were adapted and transferred.38,39 Hence, red porphyrin fluorescence was observed with a 455 nm long-pass filter upon excitation with violet-blue (375 to 440 nm) xenon light, and also quantitatively assessed by analysis of fluorescence spectra.40 Fluorescing and nonfluorescing samples taken from the tumor perimeters were examined histologically. Normal brain tissue revealed no porphyrin fluorescence, whereas tumor tissue was distinguished by bright red fluorescence. For a total of 89 tissue biopsies, the sensitivity was 85% and the specificity was 100% for the detection of malignant tissue. For seven of nine patients, visible porphyrin fluorescence led to further resection of the tumor. Photobleaching caused a decay of the fluorescence intensity to 36% in 25 min during violet-blue light excitation and in 87 min during white light exposure. These observations suggested that 5-ALA induced porphyrin fluorescence may label malignant gliomas safely and accurately enough to enhance the completeness of tumor removal. Concurrent developments of neurosurgery-specific optical devices, aimed at improving such fluorescence-guided microsurgical resections of malignant gliomas using surgical microscopes, finally enabled uncomplicated and rapid recognition of the red tumor fluorescence and its borders to normal tissue, without interrupting the course of the surgery. Such systems appeared to constitute a useful tool for optimizing removal of malignant gliomas on a routine basis.41,42 Hence, prospective clinical trials involving the fluorescence-guided resection (FGR) technique based on 5-ALA induced PPIX fluorescence were started.37,43,44 This technique has meanwhile been evaluated in multicenter clinical trials, and it is nowadays established in a variety of neurosurgery hospitals.43 So far, 5-ALA based FGR in neurosurgery is approved in Australia, Hong Kong, Israel, Taiwan, South Korea, and Japan.

However, even when employing FGR based on 5-ALA induced PPIX, which had proven to exhibit excellent sensitivity and specificity and to considerably facilitate “gross total tumor resections”4548 as shown in Fig. 3, one cannot expect the surgery to be curative, due to the infiltrative nature of the tumor growth.37

Fig. 3

(a) Red fluorescence of 5-aminolevulinic acid induced protoporphyrin-IX during fluorescence-guided glioblastoma multiforme resection serves for contrast enhancement and allows demarcation of residual tumor tissue with millimeter resolution, thus offering surgeons a precise guidance during resection.48 (b) Intraoperative white light view of the same situation.



Photodynamic Therapy

Apart from the specific induction of tissue fluorescence, fluorophores such as PPIX may also cause the tissue to be photosensitized. PDT relies on the accumulation of significant amounts of such photosensitizing agents in the diseased tissue, which in combination with properly designed light exposure leads to phototoxic effects in the treated tissue. PDT is increasingly being used amongst health practitioners in combating a variety of diseases.49 In the field of 5-ALA based PDT, a variety of clinical approaches are either under investigation or in clinical trials, which include the areas of dermatology, urology, brain, otorhinolaryngology, gynecology, and gastroenterology. In the following, the translation of basic scientific investigations to clinical application is sketched for the case of neurosurgery.

In vitro and in vivo investigations showed the potential of 5-ALA induced PPIX as photosensitizer for PDT in C6 glioma cells.5052 This suggests that the PPIX content in tumor tissue observed during FGR could also be exploited for PDT treatment of glioblastoma, both by surface irradiation of the surgical cavity and/or by stereotactically guided interstitial irradiation. These treatment modalities could be particularly helpful when clinical tumor removal by FGR had to be finished prematurely even though not all red or faintly fluorescing areas had been resected, e.g., because the affected tissue regions were part of eloquent areas. Intraoperative fluorescence spectroscopy showed higher sensitizer concentration in vital brain tumor versus the infiltration zone and in the infiltration zone versus adjacent normal brain, which contained very little PPIX.53 Obviously tumor cells in the infiltration zone can be reached by PDT, which would otherwise be left behind untreated.

While PPIX based PDT is well-established for the treatment of actinic keratosis and basal cell carcinoma,54 there are only occasional clinical reports about its application for GBM treatment.55 Even in these cases, the photosensitizer Photofrin® has mostly been used in addition, obviously because the surgeons were not trusting in a sufficient phototoxic potential of the accumulated PPIX from 5-ALA alone. A variety of different photosensitizers have meanwhile been investigated for intracranial PDT56, 57including metronomic PDT.58,59 Published clinical experience with PDT for GBM treatment relying solely on 5-ALA induced PPIX is limited.6064 In these trials and individual treatment attempts, PDT was applied by interstitial placement of radial diffusers while relying on the same or only slightly increased 5-ALA dosage as usually used for FGR.

Successful PDT requires homogeneous irradiation and light detection for dosimetry purposes. Irradiation devices for focal PDT of the brain cavity after FGR of the tumor tissue had been developed,65 and the accumulation of PPIX in the brain tumor and adjacent tissue had been investigated to improve the PDT effect61 before interstitial PDT (iPDT) could be applied clinically for the first time.66

Limited knowledge about the light, temperature, and photosensitizer distribution within the target volume initially hampered the clinical application of iPDT of gliomas. Monte Carlo (MC) simulations of fluence rate and heat transport resulted in an improved three-dimensional (3-D) treatment planning, which allowed to assess and define the treatment volume more accurately and to optimize the position of the light diffusers within the lesion.60 Optical needle endoscopy was implemented for safe and precise stereotactically guided biopsy sampling in neurosurgery, which may also provide an innovative means to further optimize and individualize the iPDT treatment in the future.67

Overall, stereotactic iPDT in combination with treatment planning could be shown to be a safe and feasible treatment modality.66 These single-case treatments were extended to also include on-line monitoring of PPIX fluorescence and photobleaching kinetics, which seems important as dramatically different PPIX concentration levels and photobleaching kinetics have been observed. Such data were assessed and analyzed in order to employ them for real-time treatment monitoring and as early prognostic markers for the PDT response of individual patients. With regards to the PPIX concentration, it could be shown that necrotic regions typically located in the center of a GBM tumor are characterized by significantly lower PPIX levels than the outer regions consisting of vital tumor tissue. As indicated by this example, the implementation of fluorescence spectroscopy during iPDT could become a promising tool for individualized treatment concepts.61,68,69 The evaluation of such spectroscopic data obtained from interfiber measurements of fluorescence and transmission during clinical stereotactic iPDT showed that the intratumoral PPIX concentration in glioblastoma exhibits pronounced inter- and intratumoral variations, which are directly linked to likewise variable levels of fluorescence intensity.64 A high intratumoral PPIX concentration, associated with strong fluorescence intensity and complete photobleaching in the course of an iPDT treatment, also seems to be associated with a favorable treatment outcome. A typical intraoperative situation during an iPDT treatment with real-time monitoring of PPIX fluorescence intensity and photobleaching is shown in Fig. 4. The monitoring procedure turned out to be feasible and might be suitable for early treatment prognosis of iPDT. Furthermore, an individualization of treatment strategy and treatment parameters based on this information appears to bear a potential to further improve the clinical outcomes.64,70 Improving all these techniques and the interaction between highly motivated partners may improve the clinical situation for treating GBM in neurosurgery for the benefit of the patients to prolong symptom-free survival with the highest degree of quality of life.63

Fig. 4

Clinical stereotactic interstitial photodynamic therapy using several fibers ending in cylindrical diffusors for therapeutic light application (e.g., 635 nm). The system is capable of interfiber detection of fluorescence (e.g., 705 nm) and transmission (e.g., 635 nm) for on-line monitoring during treatment.64,70



Diagnostics/Treatment of Breast Cancer


Challenge in the Clinical Management of Breast Cancer

BC remains the most common oncological disease for women in North America71 and worldwide.72,73 The challenges BC presents for health care systems and the affected individuals are different in high-income countries where BC screening and therapy are well-established compared to low- and middle-income countries where, particularly for the latter, mammographic screening remains a bottleneck leaving women often nondiagnosed.

In high-income countries, the combination of high participation in mammography screening programs72 in combination with advanced therapeutic options have led to a high five-year survival of >90%, for BC patients.71 In particular, the advanced treatment options comprising surgery, chemotherapy (prior to surgery and postsurgery), and radiation therapy resulted in statistically equal five-year survival times for a nonscreened and a mammographic screened population. This opens the doors to different interpretation concerning the need for mammographic screening. While lowering screening compliance will result in more late-state tumors, it will also reduce overdiagnosis, thus reducing stress and unnecessary secondary testing, including invasive biopsies in false-positive women. Conversely, the treatment of late-stage BC will increase costs 20 to 30 times74 more than that of stage I/II BC. Additionally, survival statistics beyond five years are not available with adequate repeats to generate final recommendations about BC screening’s efficacy. Conversely, while 40- to 50-year-old women have an overall low incidence of BC,72 their incidence rates are increasing at the highest rate particularly in countries undergoing a lifestyle change, which is well-documented in South Korea75 and also seen in countries such as Mexico and Egypt, although with less-solid data. It is in particular this age group that benefits of the most from early detection of BC as they would face potentially the most life years lost. Hence, improving the selection of women entering a BC screening program and adjusting the screening frequency based on a personalized risk assessment will lead to a better utilization of available screening resources in low- and middle-income countries and hence enable detection of predominantly early-stage BC, thus simultaneously reducing the overall cost burden to these health care systems.

Photonics-based tools for BC detection are still required particularly for premenopausal women and women with high mammographic tissue density as dense glandular and connective tissue hinders the detection of small lesions in the breast. While high-risk BrCa I/II gene mutation carrier are typically imaged every six months, alternatingly with MRI or ultrasound (US), other high-risk women, particularly those with a strong family history of BC or on long-term immune suppression therapy for an unrelated disease, are not given the same considerations. Nonionizing low-cost imaging-based screening is highly desirable for this population. The requirements for these imaging modalities are providing high contrast between glandular and, in particular, malignant tissue, being mostly independent of connective and fatty tissue. Low cost is desirable for implementation of this technology as standard BC screening technology, particularly in higher-mid- to lower-high-income countries with pending implementation of a national BC screening program, is an urgent task as these countries also currently have the largest gains in life expectancy and, hence, overall increase in BC incidence. Here again if the situation from Korea and Japan repeats itself, the increase will be disproportional in women <50years of age who are commonly not captured by x-ray based BC screening. It is noteworthy that this is an economically limited environment, although it encompasses up to 1/4 of the female world population. The needs of these women pertaining to BC screening and early detection are unlikely to be met with current x-ray based technology including tomosynthesis as this is aimed primarily on the highest-income countries; see Table 1 (modified from Ref. 76).

Table 1

Breast cancer screening programs in 26 ICSN countries in 2012.

Region/countryYear program beganDetection methods in routine useAge groups coveredRecommended interval for average risk for mammographyNumber of women screened (2010)Participation rate (2010) age 40 to 49
Australia1991MM, DM40 to 75+2 yearsData not availableData not available
Canada1988MM, DM, CBE50 to 691 year196,18747.30%
China2009MM, CBE, U40 to 593 years1,200,000Data not available
Denmark1991DM50 to 69NA275,00073.00%
Finland1987DM50 to 64NAData not available85.00%
France1989MM, DM, CBE50 to 74NA2,343,98052.30%
Iceland1987DM, CBE40 to 692 yearsData not available60.00%
Israel1997MM, DM50 to 74NA220,00072.00%
Italy2002MM, DM50 to 69NA1,340,31160.50%
Japan1977MM, DM, CBE40 to 75+2 years2,492,86819.00%
Korea1999MM, DM40 to 75+2 years2,602,92839.30%
Luxembourg1992DM50 to 69NA14.58664.00%
Netherlands1989MM, DM50 to 74NA961,76680.70%
New Zealand1998MM, DM45 to 692 years211,92267.50%
Norway1996DM50 to 69NA199,81876.00%
Poland2006MM, DM50 to 69NA985,36439.00%
Portugal (Central Region)1990DM45 to 692 years100,34863.00%
Portugal (Alentejo Region)1997DM45 to 692 years7298Data not available
Saudi Arabia200740 to 64620019.00%
Spain (Catalonia)1995MM, DM50 to 69NA527,000Data not available
Spain (Navarra)1990DM45 to 692 years40,01687.30%
Sweden1986MM, DM40 to 7418 months1,414,00070.00%
Switzerland1999MM, DM50 to 69NA60,70048.20%
United Kingdom1988MM, DM50 to 691,957,12473.30%
United States1995MM, DM, CBE40 to 75+1 to 2 years416,00066.50%
Uruguay1990MM, CBE, U, BSE40 to 692 years352,000Data not available
Note: Data are from a survey of International Cancer Screening Network (ICSN) country representatives, conducted in 2012.76 MM, screen-film mammography; DM, digital mammography; CBE, clinical breast exam; BSE, breast self-examination; U, ultrasound.

A field where an adoption of photonics-based imaging tools is anticipated and highly likely is for neoadjuvant chemotherapy outcome prediction, where the therapy is limited to a very short time span due to the commonly advanced nature of the breast-invading tumor. The physician needs confirmation that the chosen chemotherapeutics are effective in shrinking the tumor volume or affecting its metabolism already after one or two cycles. As spatial resolution is secondary and the overall tumor response is desired, a low spatial resolution technique yet nevertheless with high contrast to changing oxygen consumption or vascularity can suffice.

Similarly to diagnostic technologies, therapeutic approaches show a significant qualitative difference between high- and middle-income countries on the one hand and low-income countries on the other hand. It is particularly evident in the latter group where the changing population age-pyramid coincides with rapidly changing environmental exposure. Middle-income countries try to emulate high income countries in their approach to treat advanced BC, which comprises neoadjuvant chemotherapy, surgery, intensity modulated radiation therapy, and chemotherapy with tyrosine or aromatase inhibitors. These treatment approaches pose a tremendous strain on the health care systems of middle-income countries, and they are generally not affordable for low-income countries. Hence, the majority of the women in low-income countries are not offered therapy, which is often further enhanced by a stigma with which these women are associated due to a BC diagnosis.

Hence, there are plenty of opportunities for novel enabling technologies to fundamentally change the clinical management of BC in high-income countries as well as low- and middle-income countries, so the technologies introduced into these markets will be different.


Optical Technologies Aimed at Improving BC Risk Assessment, Diagnostics, and Response Prediction

Various demographic- and lifestyle-based BC risk assessment tools have been developed, such as the Gail breast cancer risk assessment model or familiar risk models,77,78 and shown to be of utility for some screening decision making. However, their predictive power or odds ratio hovers below 2, and hence, they are not of utility to adjust entry and frequency of standard screening programs for the entire female population. An additional significant impediment of these risk assessment techniques is that some required predictors are not available until women are of standard mammographic screening age, missing the population of the sub-40- to 50-year-old women.

Risk assessment based on physical risk factors, analogous to blood pressure measurements for cardiovascular, cancer, and other diseases, does not face these limitations. To this effect, there is ample research showing that mammographic breast density (MBD) is one of the strongest risk factors, reaching odds ratios of up to 6 for two-dimensional mammographic projections when evaluating the top 25th percentile versus the lowest 10th percentile.79 For 3-D assessment of the mammographic density, odds ratios up to 10 are anticipated, which suggest a causal relationship between MBD and BC.80 When considering personalized oncology, the use of MBD has not progressed beyond recommendations to reduce the screening frequency for women with low MBD, so MBD is not suitable as a criterion for entry into a standard screening program. MBD cannot overcome the limited access to BC screening programs in low- and middle-income countries and as such does not overcome one of the major bottlenecks in BC management worldwide.

The risk assessment for a prescreening technology to be of utility in BC management in high-income countries needs to provide extremely high sensitivity comparable to mammography for the equivalent MBD and good specificity, as this is only a prescreening technology and the screening entry and frequency are to be personalized. In settings with limited access to standard screening technology, the main obligations are to identify the appropriate fraction of the population to advance to mammographic screening, thus optimizing the infrastructures for the women at highest risk. If the instrument is affordable, it can be shown that such a program is financially self-sustaining. For example, reducing the stage III/IV tumor incidence in countries with population of >100 million from the mid-30% to <15%, entirely attainable when the available infrastructure approximates the OECD guidelines of 12 mammographs per 1 million BC cases, treatment costs can be reduced by over 300 to 500 million USD/year depending on the actual population size and the female life expectancy. Optical prescreening (Fig. 5) would be built on the intrinsic breast tissue optical properties using either absorption81 or fluorescence properties82 or both,83 or on optical coherence spectroscopy.84

Fig. 5

(a) Principal optical components for transmission measurements (left) and setup with four quadrants identified on the right breast (right). The small insert shows the tissue during measurements. (b) Optical density (OD) per physical optode separation (or relative optical density) in units of 1/cm for women with high (left) and low (right) mammographic breast density (MBD), respectively. (c) Chemometrix (principal component analysis) score based clustering of high MBD and low MBD.


Here, in particular, the work of the Turino85,86 and Toronto81,8789 groups have demonstrated the ability to identify women with known physical risk factors, such as MBD79,90,91 or biological event linked to the development of breast cancer, such as glandular atrophy during permenopause and postmenopause.92 While it is not clear at this time what fraction of the BC can be attributed to these different risk factors, however, the differences in the breast composition are accessible optically. Contrast is provided by the wavelength-dependent absorption spectra of predominantly water, lipid, hemoglobins, and collagen as well as by changes in the light scattering coefficients. The risk to develop BC does not correlate with particular tissue substructures, and hence spatial resolution is not required. The Toronto group favors steady-state spectrally resolved diffuse reflectance measurements, using either only chemometrix analysis, such as principal component analysis, for disease classification93,94 or quantitative tissue chromophore extraction building on prior work by Farrell et al.95 to first extract the spectral absorption and scattering coefficient followed by least-square fitting to derive the chromophore concentrations. The Milano group favored the use of time domain measurements to extract chromophore concentrations, allowing an analytical determination of the spectrally resolved light transport parameters preferable in establishing relationships of optical properties and known BC risk factors and future incidence of BC.

The ability to identify women with high MBD has been demonstrated for a screening aged population with sensitivity and specificity >0.9 when combining with menopausal status and body mass index by the Toronto group9698 and a p<0.0001 to differentiate a BIRADS 4 scores indicative for high MBD versus lower BIRADS scores by the Milano group.85,86 Strong correlations have also been demonstrated for other risk factors, such as parity, age, and menopausal status.87,89

For immediate application in low- and middle-income countries, robust and low-cost solutions, possibly based on cw measurements, are preferable as long as they satisfy the sensitivity and specificity requirements in identifying the subpopulation at highest risk to benefit from the screening infrastructure. High sensitivity and specificity >0.8, sufficient to be subsequently screened by butting national screening programs, can be achieved only using relative spectra shape, and thus, absolute instrument calibration is not required, facilitating the use of these instruments in resource-limited environments.

Optical tools are also being investigated to predict treatment response, in particular, for neoadjuvant chemotherapy, during the initial work therapeutic session to determine if a particular chosen treatment regime has the desired effect toward shrinking of the tumor to render it amendable to therapy. In particular, frequency domain spectroscopic scanning or tomographic approaches are being developed by various groups.99107 However, frequency domain optical tomography has demonstrated only limited utility as a screening tool due to its limited spatial resolution,108 even when using a large number of source and detector pairs. Using added information, such as spatial information about the distribution of fatty versus glandular tissue from clinical imaging and knowledge of the chromophores’ absorption spectra demonstrated,109111 does not significantly improve the resulting spatial resolution in order to detect early-stage cancers at a rate comparable to current clinical imaging technologies even in premenopausal women. While some of the technology is comparable to that described previously for risk assessment, the number of source-detector pairs is commonly larger to achieve some spatial localization of the contrast. As vascular normalization is a primary goal of neoadjuvant chemotherapy, pruning of the aberrant vascular tree will modify the total hemoglobin concentration as well as the oxygen saturation in the affected tissue volumes.106,112 During initial clinical studies, it was demonstrated that correct response prediction was achieved and that the hemoglobin contrast to normal tissues exceeds a ratio of 2.

Photoacoustic imaging, as for example developed by the Twente group with their photoacoustic mammography,113 is promising as a screening alternative, particularly for premenopausal women where tumors are masked by high mammographic density as shown in a comparative study versus MRI.114 Contrast is relying on the angiogenesis associated with tumor development for the selective absorption contrast. As absorption is mostly independent of the structures, providing high MBD photoacoustic mammography is also applicable in premenopausal women. In a recent small clinical study, Kitai et al. demonstrated the ability to detect all cases of ductal carcinoma in situ and most tumors that underwent prior neoadjuvant chemotherapy.115

The lower technical complexity of photoacoustic imaging over diffuse optical tomography makes it possibly the preferred technology independent of the available health care resources.

To summarize opportunities in the management of BC, the field of risk assessment or prescreening has significant potential particularly for younger women at risk. Here photonics-based diagnostics may complement US- or MRI-based assessment and/or preselection of women at risk of developing or harbouring BC in a resource-limited environment. Photoacoustic imaging can also become a valuable tool for BC detection, whereby monitoring of neoadjuvant chemotherapy by diffuse optical tomography should be considered whenever this therapy is offered.


Photonics-Based Therapeutic Solution

As mentioned previously, there is indirect evidence that the current decrease in BC-related mortality in high-income countries is predominantly due to improved therapeutic efficacy and the present move towards personalized cancer medicine. The number of targets for BC is constantly increasing ranging from tyrosine and protein kinase inhibitors, epigenetic regulations, and nanomedicine with several of these approaches being introduced particularly in high-income countries. However, independent of the various therapies offered to the patient, surgical removal of the primary tumor is the standard of care, and its efficacy is limited by the need to demonstrate tumor-free resection margins. In a simplification to the use of FGR of brain tumors described previously, in BC, significant wider resection margins are acceptable,116 reducing the need for quantitative assessment of fluorescence. In general, the aim is a move towards near-infrared fluorescence in order to capture nests of infiltrating tumors several millimeters below the resection cavity surface.117,118 Clinical trials for indocyanine green (ICG) fluorescence are ongoing, so primary data have not been published119 to date.

A second clinical application for fluorescence guidance is the intraoperative detection of sentinel lymph nodes using ICG as contrast medium120,121 with or without active targeting, or intensely staining blue dyes. The first published multicenter clinical trial122 demonstrated an equal detection ability compared to radiolabeling or blue dyes. This was also confirmed by a recent meta-analysis123 suggesting equal performance between fluorescence and radiolabel detection.

An alternative to surgical removal of the primary tumor was evaluated using either PDT124,125 or photothermal applications, such as with interstitial laser photocoagulation32,126128 and interstitial laser hyperthermia.129,130 Particularly the photothermal ablation models are currently not being researched as it becomes increasingly evident that complete surgical resection or ablation of the primary tumor will lead to high five-year survival rates, but without an immune effect introduced, a long-term survival is not guaranteed.131 More recent research is focusing on the therapy of metastatic BC particularly with spinal and bone involvement.132

An interesting photon generation solution was proposed by Batista and Liang using solar irradiation, which could potentially have utility in extreme resource-limited environments when the primary tumor is to be destroyed in situ.133

In summary, particularly supporting surgical lumpectomy by fluorescence-guided resection and detection of tumor infiltrated lymph nodes currently appear to be the most promising avenues for photonics solutions in the management of BC. Removal of the primary tumor is currently still best achieved with surgical resection followed by the various chemotherapies and radiation therapies aimed at treating the remaining micro metastasis and preferably also inducing the desired immune response.


Treatment of Hyperplastic Nasal Turbinates

Inferior turbinate hypertrophy is a common cause of nasal airway obstruction. Patients that are refractory to conservative pharmacological treatment require surgery, often accompanied with long-term bleeding and further discomfort. Surgical techniques including total or partial turbectomy, laser surgery, electrocautery, cryosurgery, and radiofrequency ablation are available.134 Endonasal laser treatments cause limited side effects with little or no bleeding while similar tissue reduction could be obtained, thus reaching high patient acceptance.135138 Since the early 1980s, various types of laser systems have been developed for surgical endonasal applications. Systems for clinical applications include the CO2, Nd:YAG, Ho:YAG, KTP, as well as diode lasers of different wavelengths.139 Generally, different laser parameters (power, energy) and application modalities (contact, noncontact, interstitial, superficial) were used.139

Dependent on the laser wavelength and the associated different optical parameters of the tissue, the light-tissue interaction varies in terms of amount of coagulation and ablation volumes. Most of the commonly available diode laser systems provide light at wavelengths of λ=800 to 1000 nm, mainly causing coagulative tissue effects when applied in noncontact mode. In comparison to CO2 and Nd:YAG lasers, diode lasers have lower acquisition and maintenance costs and are more versatile in the clinical setting due to their smaller size. Recently, laser systems emitting in the spectral region between λ=1300 and 2100 nm became clinically available and were tested for this application.


Endonasal Laser Treatment

After topical anesthesia [e.g., 4% tetracaine and 0.5% xylometazoline solution (11), 10 to 15 min) photo- or video-documentation via a rigid endoscope should first be performed. Prior to introduction of the laser light application system, laser safety precautions are mandatory. Conveniently, laser light should be applied in noncontact mode using a flexible silica bare fiber (core diameter: 400 to 600μm) guided via a device for precise endonasal fiber guidance.140 Laser parameters setting need to be adjusted with respect to the laser emission wavelength [e.g., 8 to 12 W for 940 nm,141,142 4 to 5 W for 1470 nm,141143 2 to 4 W for 1940 nm.144 So far, diode lasers emitting at 900 to 1000 nm are in clinical use. Maneuvers for energy application itself should be performed via guiding the fiber from the posterior to the anterior free edge of the inferior turbinate under endoscopic control until adequate blanching of the tissue is obtained as judged by the operating surgeon. In cases where the head of the inferior turbinate appeared to be especially prominent, only some single laser spots were directed onto the head of the turbinate. Postoperatively, nasal cavities were treated with antibiotic and steroid-containing ointment (e.g., Jellin-Neomycin®: 0.25 g fluocinolone acetonide / 4.25 g neomycin sulfate). Patients received prescriptions for nasal ointments and nasal decongestants.

A typical outpatient laser-assisted inferior turbinate reduction of the hyperplastic inferior turbinate using a Tm:fiber laser emitting at 1940 nm at 3 W using a fiber guidance system is shown in Fig. 6, prior to, immediately after, and two months after treatment.144

Fig. 6

Outpatient therapy for laser-assisted inferior turbinate reduction of a hyperplastic inferior turbinate using a Tm:fiber laser emitting at 1940 nm at 3 W using a fiber guidance system.144 (a) Endonasal situation prior to laser energy application without decongestion showing the turbinate hindering continuous airflow, (b) immediately after laser energy application coagulation could be observed, and (c) two months after laser treatment the reduction of the turbinate is obvious (without decongestion) and continuous airflow is possible.



Clinical outcome of Endonasal Laser Treatment Studies

Investigations and clinical trials show the safety and efficacy of laser treatment for volume reduction of hyperplastic turbinates in single cases as well as in prospective, randomized, and blind studies. The macroscopically visible tissue effect depends on the wavelength used. Observations by the operating surgeon on the basis of tissue whitening and tissue reduction confirm that 1940 and 1470 nm irradiation was about equivalent to the effects of the commonly used 940 nm laser system, yet it required a reduced irradiance, a significantly shorter treatment time, and less total energy.141143 These treatment procedures could be performed as an outpatient procedure under local anesthesia, and therefore, the patient acceptance and satisfaction were exceptionally high. The overall pain sensation was very moderate, with a trend towards less intraoperative pain using the longer wavelengths.141 Neither minor nor major complications could be witnessed in these studies during operation as well as postoperatively.145147 The main symptoms due to hyperplastic inferior turbinate (nasal congestion and nasal obstruction during exertion) could be significantly improved. Correspondingly, a significant symptom improvement was also shown in the validated assessment tool SNOT 20 GAV (“need to blow nose”).141,144

Especially the long-term outcome seems to be the critical issue with the laser treatments of the turbinates.139,148153 Moreover, there is currently no clear consensus or gold standard in the literature indicating the most optimal technique for turbinate reduction.139,154157 This lack of a gold standard renders an appropriate evaluation or a comparison of novel techniques challenging. Nevertheless, laser-assisted and radiofrequency-assisted reduction of hyperplastic turbinates seem to be standing out as methods that can be applied under local anesthesia providing minimal morbidity.139 For these reasons, the 940 nm diode laser was used for more than a decade for this indication and is regarded as the standard laser application.139,145,146,152

With regard to lowering the applied irradiation, medical devices emitting at 1940 nm should be preferred, but these are rarely available in hospitals. As the 1470 nm diode laser systems are more widespread, these systems offer a highly efficient alternative to conventional diode laser systems in treatment of nasal obstruction due to hyperplastic nasal turbinates. In therapy-refractory rhinitis medicamentosa, outpatient diode laser inferior turbinate reduction of hyperplastic inferior turbinate represents a highly effective, safe, and well-tolerated treatment option that provides long-lasting recovery by markedly improving nasal airflow and stopping addiction to nasal decongestants.158 It had also been shown that rhinomanometry with topical decongestion has a high predictive value for the objective outcome of laser-assisted turbinoplasty.159

In conclusion, laser surgery of inferior turbinates can be performed as an outpatient procedure under local anesthesia. Due to a minimally invasive and controllable coagulation and ablation of soft tissue, almost no complications or bleedings were observed during the operation or postoperatively. Depending on the chosen parameters (power, energy) and the application modalities, laser treatment of hyperplastic inferior nasal turbinates achieved comparable or better results than most of the conventional techniques for turbinate surgery, like conchotomy, electrocautery, cryotherapy, chemical cauterization, and vidian neurectomy. Laser treatment can be considered a useful, cost-effective, and time-saving procedure for the reduction of hyperplastic inferior nasal turbinates. Short operation time, good clinical outcome, and minor side effects compared to other surgical methods provide an excellent clinical response of the patients.


Endovenous Laser Treatment of Varicose Veins

Varicose veins are widened vessels due to weakened connective tissue and insufficiency of vein valves. In middle Europe, the incidence is 50% (age: 20 to 75) with a female / male ratio of 2 / 1). Located on the lower extremities, the symptoms are subjectively described as sensations, such as heavy legs, tension, swelling, pain while standing and sitting, discoloring, and phlebitis. The involved structures are mainly the vena saphena magna (VSM) and the vena saphena parva. In half of the cases, patients need surgical intervention with the main goal of complete destruction of the vessel. Besides methods of conservative surgery and stripping treatments during the last 15 years, endoluminal procedures like sclero-therapy, radio-frequency ablation, and endovenous laser therapy (ELT) have gained attention among the medical community. Figure 7(a) shows the principle of a clinical ELT treatment of the VSM of a right leg. Typically, the physician pulls the fiber backward at a velocity of 1mm/s while the assistant is imaging the endoluminal location of the fiber by means of US. By means of US, the laser energy induced thermal effects can also be visualized as shown in Fig. 7(b).

Fig. 7

(a) Clinical situation for endovenous laser therapy treatment of vena saphena magna of a right leg. Veins and perforators are marked in black on the skin. The medical doctor (left two hands) pulls the fiber backwards at a velocity of 1 mm/s. The assistant (right two hands) positions the ultrasound (US) head to image the endoluminal location of the fiber (red light transmission of the pilot beam through the skin is obvious). (b) US image of the location and the state of the vein. In the left part, the vein lumen is closed by thermal shrinkage while the fiber is still in the lumen. In the right part, the lumen is still not affected by laser energy; thus, the lumen is widened.


The first clinical results of ELT were published in the beginning of this millennium.160,161 The endothermal damage of the vein wall arises from thermal shrinkage of connective tissue and thermal denaturation by coagulation induced shrinkage of the lumen and consecutive occlusion of the treated vein.162168 The clinical outcome looks very promising. Meta-analytic studies give evidence that these innovative techniques result in a similar clinical outcome as conventional surgical stripping.169175 Currently the laser medical equipment is still under development. One disadvantageous characteristic of ELT is the broad spectrum of different treatment protocols using a variety of laser systems and devices for endovenous application. Recently, systematic experimental investigations and analyses of clinical results have increased the knowledge of the relation between particular details of endovenous laser application and clinical results.162,165,168,176

Due to the diversity of laser parameters (e.g., wavelength, light application system, power, irradiance, irradiation) and the corresponding variable interaction with the target tissue, physicians request for a precise, reproducible, safe, standardized procedure and treatment protocol,177180 which includes the strategic investigation of light application systems168,176,181 as well as potential on-line feedback.


Endovenous Light Application

The endovenous laser treatment relies on the transformation of luminous energy into heat due to absorption. This process depends on the wavelength-dependent optical properties of the tissue and can be investigated by MC simulations.182185 Thus, the endoluminal application of laser energy implies the necessity of controlling a variety of parameters all together influencing the alteration produced on the vein wall. Variations in the laser wavelength, power settings, and irradiance result in different temperature levels and thermal alterations up to perforation.182,183,186188 As blood is the primary medium around the laser fiber tip, it influences the mechanism and the alteration process as well, especially in cases where carbonization is induced.162,164,181,189

Initially, laser energy was applied by using bare fibers emitting coaxially in the vessel lumen. The approach was the development of a specific radial emitting fiber to deliver the energy in direction to the vessels wall.167,168,176,190 In dependency of the used wavelength, the transmission through the existing thin blood layer around the fiber tip differs. As shown in Fig. 8, irradiation pattern showed maximum intensity deflected in an angle of 70deg without any axial irradiance transmission. The measured transmission efficiency of such device was 94 to 97%. In comparison to the bare fiber technique, the irradiance (if contact to the tissue is assumed) can be reduced by a factor of 7 to reach irradiance values just below the ablation threshold of tissue.168,176

Fig. 8

Radially emitting fiber and its irradiation characteristics.


In tests of the radial fiber technique on an ex vivo vein model167 using heparinised blood containing veins, a shrinkage in length, a thickening of the wall, and the increased rigidity assessed by digital inspection could be achieved perfectly without any perforation.167,168,176,190 Additional investigation of the wavelength dependency of this treatment also showed that using a laser emitting at 980 nm an output power of P980=(20±2)W is needed to achieve the desired macroscopic tissue alteration. In contrast, for a 1470 nm emitting diode laser, an output power of P1470=6 to 8 W is only necessary to achieve the same macroscopic results. On inspection of the surgically opened lumen of the vein, charred blood clots could be observed in the case of 980 nm irradiation, whereas in case of 1470 nm irradiation, a clean white coagulated vein intima surface was observed.167,168,190 Further investigation also showed wavelength-dependent discrepancies.186,191 These effects are clearly related to the wavelength-dependent optical properties of vein tissue and blood189 and were confirmed by MC simulations.182185

Heat induction (T=85°C for 30 s) of the vein tissue samples showed a swelling of the sample concomitant with shrinkage in length. Additionally, the reddish vein color changed to whitish color of denatured tissue. The feeling sensation changed from flexible, smooth, and elastic to rigid and “macaroni-al-dente-like.” Vein tensile experiments showed native veins are elastic and can be stretched with low tensile power up to rupture, while cooked veins are inelastic and high tension powers are necessary for rupture. Both factors may explain patients’ description of having stretch discomfort after ELT.167,168,190

Technologies such as the 360 deg radial fiber in combination with 1470 nm laser light168,192 look promising as a means to induce safe, reliable, and reproducible tissue alteration for the ELT. By means of these optimizations, ELT treatment is getting closer to the goal of standardizing an effective method for the treatment of varicose veins. In a variety of investigations, disadvantages of previous ELT application techniques could be shown.168,187,188 The introduction of the more effective wavelength and the new radial procedure has been established in clinical use since 2009.193,194 First clinical studies show a clinical benefit.195200 Today, long-term follow-ups confirm the persistent effectiveness and safe occlusion of the veins.201 Based on the reduction of undesirable side effects and the accelerated convalescence, endovenous treatment methods became the treatment option of first choice for insufficient veins in some countries.202,203 Despite these improvements, some minor effects like carbonization and adhesion of the fiber to the vessels wall could still be observed during the clinical procedure. Therefore, implementation of feedback technologies may further assist standardization of the procedure.


On-Line Monitoring During ELT

Although endoluminal techniques are medically approved and the clinical outcome of endoluminal treatments are accepted by physicians, due to meta-analysis of a large cohort studies,204210 as well as by the patients there are still requests for further improvement as adjacent structures should be prevented from temperature-related changes. Currently, real-time monitoring of physical, physiological, and tissue conditions is not available. Feedback information may have the potential of controlling the treatment or supplying immediate hints for the success of the treatment.

Tissue effects that could be optically detected in principle are shrinkage of the lumen, white light remission of the vessel wall, autofluorescence of the vessels wall, and temperature on the tissue or at the fiber tip. Investigations were performed to develop systems for endoluminal in vivo on-line monitoring of such parameter, during laser energy application and within the irradiation field.176,211

MC simulation of optical detection of the shrinkage effect looks promising only for small vessel calibres. Using the radially emitted light of wavelengths between 600 nm (pilot beam) and 1500 nm (therapeutic wavelength), which is reflected by the vessels wall and then detected by the same fiber, showed that the moving vessel wall can only be detected when the distance between the fiber and tissue is <2mm in case of being filled with pure water and <1mm in case of the presence of blood. As native and coagulated vein tissues differ in their optical properties, the white light remission spectrum changes its shape during the denaturation process accordingly. Unfortunately, in the presence of blood, white light remission measurements as well as in situ measurements of autofluorescence are challenging. Finally, a temperature measuring system based on the analysis of the temperature-dependent fluorescence of a ruby crystal is developed.211 This sensor can be manufactured such that it is inert and biocompatible. It was tested to be useable in a high electromagnetic field, such as within the laser light irradiation field. Temperatures ranging from 20 to 200°C could be measured with an accuracy of ±2°C. Clinically adapted ex vivo experiments in a blood filled vein showed accurate measurements when the sensor tip is positioned in the vein parallel to and directly within the radially-emitting therapeutic fiber.211

In conclusion, the suggested technical feedback improvements are not yet clinically available. As visual control of the immediate tissue effect, such as lumen shrinkage or vein wall thickening, extra corporal UA and photoacoustic techniques are suggested but used from the skin surface. Additionally, the control of the pullback velocity of the treatment fiber and the irradiation parameters may yield improved light dosimetry. Implementation of a local endoluminal temperature may yield an improved reliable and successful treatment for the benefit of the patient.



Research and development in laser medicine and biophotonics is very dynamic and continuously expanding. National and international presentations induce critical discussions between members of the scientific and medical communities. These sessions are key opportunities and are highly necessary to identify and explore unmet clinical needs and detailed requests from clinicians. The incorporation of technicians and companies is indispensable to support the development of prototypes and to start clinical trials. Unfortunately, only after clinical testing, sometimes in comparison to established nonoptical clinical procedures, the impact of new biophotonic technologies on clinical application becomes obvious, in a positive or negative way. This constitutes one example of a multiplicity of barriers that need to be conquered before achieving clinical application and, finally, full acceptance in the medical community. The collection of conference-related references cited in this article may indicate that long-term highly motivated research and development is necessary to reach clinical success. Furthermore, the presented examples clearly show that knowledge about the requirements of physicians in their clinical work is the basis for beneficial technical developments. The transfer of scientific knowledge into components and systems with either new or improved properties may then allow researchers to create new innovative tools to support clinicians in their clinical practice.


The authors would like to thank all coworkers, technicians, and students who took part in the diverse projects as each and every single experiment and scientific discussion that resulted in improvements to bring new laser-based biophotonic concepts into clinical reality. The authors would also like to thank the companies for their long-term support with devices and equipment to enable the teams to perform the clinical-related research. Finally, all our sponsors and grant providers are acknowledged for financially supporting the numerous projects. There are many more examples and techniques in a variety of medical disciplines that could also be mentioned. The authors apologize for only giving insight into a small selection of successful approaches chosen from their own points of view and experiences.



G. Hennig et al., “Dual-wavelength excitation for fluorescence-based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood,” J. Biophotonics, 7 (7), 514 –524 (2014). JBOIBX 1864-063X Google Scholar


G. Hennig et al., “Dual-wavelength excitation to reduce background fluorescence for fluorescence spectroscopic quantitation of erythrocyte zinc protoporphyrin-IX and protoporphyrin-IX from whole blood and oral mucosa,” Proc. SPIE, 8951 89510J (2014). PSISDG 0277-786X Google Scholar


M. B. Zimmermann and R. F. Hurrell, “Nutritional iron deficiency,” Lancet, 370 (9586), 511 –520 (2007). LANCAO 0140-6736 Google Scholar


J. M. Tielsch et al., “Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial,” Lancet, 367 (9505), 144 –152 (2006). LANCAO 0140-6736 Google Scholar


S. Sazawal et al., “Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial,” Lancet, 367 (9505), 133 –143 (2006). LANCAO 0140-6736 Google Scholar


“Conclusions and recommendations of the WHO Consultation on prevention and control of iron deficiency in infants and young children in malaria-endemic areas,” Food Nutr. Bull., 28 (4 Suppl), S621 –627 (2007). FNBPDV 0379-5721 Google Scholar


M. B. Zimmermann, “Methods to assess iron and iodine status,” Br. J. Nutr., 99 (Suppl 3), S2 –9 (2008). BSJSE4 1057-6606 Google Scholar


F. K. Grant et al., “Comparison of indicators of iron deficiency in Kenyan children,” Am. J. Clin. Nutr., 95 (5), 1231 –1237 (2012). AJCNAC 0002-9165 Google Scholar


P. Suominen et al., “Serum transferrin receptor and transferrin receptor-ferritin index identify healthy subjects with subclinical iron deficits,” Blood, 92 (8), 2934 –2939 (1998). BLOOAW 0006-4971 Google Scholar


C. Thomas and L. Thomas, “Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency,” Clin. Chem., 48 (7), 1066 –1076 (2002). CLCHAU 0009-9147 Google Scholar


A. A. Lamola and T. Yamane, “Zinc protoporphyrin in the erythrocytes of patients with lead intoxication and iron deficiency anemia,” Science, 186 (4167), 936 –938 (1974). SCIEAS 0036-8075 Google Scholar


R. F. Labbe, H. J. Vreman and D. K. Stevenson, “Zinc protoporphyrin: a metabolite with a mission,” Clin. Chem., 45 (12), 2060 –2072 (1999). CLCHAU 0009-9147 Google Scholar


E. Rossi and P. Garcia-Webb, “Red cell zinc protoporphyrin and protoporphyrin by HPLC with fluorescence detection,” Biomed. Chromatogr., 1 (4), 163 –168 (1986). BICHE2 0269-3879 Google Scholar


B. Kaul, G. Slavin and B. Davidow, “Free erythrocyte protoporphyrin and zinc protoporphyrin measurements compared as primary screening methods for detection of lead poisoning,” Clin. Chem., 29 (8), 1467 –1470 (1983). CLCHAU 0009-9147 Google Scholar


G. Metzgeroth et al., “Zinc protoporphyrin, a useful parameter to address hyperferritinemia,” Ann. Hematol., 86 (5), 363 –368 (2007). ANHEE8 1432-0584 Google Scholar


J. Hastka et al., “Washing erythrocytes to remove interferents in measurements of zinc protoporphyrin by front-face hematofluorometry,” Clin. Chem., 38 (11), 2184 –2189 (1992). CLCHAU 0009-9147 Google Scholar


J. Hastka et al., “Zinc protoporphyrin in anemia of chronic disorders,” Blood, 81 (5), 1200 –1204 (1993). BLOOAW 0006-4971 Google Scholar


K. H. Yu, “Effectiveness of zinc protoporphyrin/heme ratio for screening iron deficiency in preschool-aged children,” Nutr. Res. Pract., 5 (1), 40 –45 (2011). NRPUBQ 1976-1457 Google Scholar


“Zinc-protoporphyrin/protoporpyrin HPLC kit: manual (preliminary),” (2011) Google Scholar


W. E. Blumberg et al., “The hematofluorometer,” Clin. Chem., 23 (2), 270 –274 (1977). CLCHAU 0009-9147 Google Scholar


R. E. Hirsch, M. J. Lin and C. M. Park, “Interaction of zinc protoporphyrin with intact oxyhemoglobin,” Biochemistry, 28 (4), 1851 –1855 (1989). BIORAK 0006-2979 Google Scholar


R. J. Stoltzfus et al., “Iron supplementation of young children: learning from the new evidence,” Food Nutr. Bull., 28 (4 Suppl), S572 –584 (2007). FNBPDV 0379-5721 Google Scholar


E. Buhrmann, W. C. Mentzer and B. H. Lubin, “The influence of plasma bilirubin on zinc protoporphyrin measurement by a hematofluorimeter,” J. Lab. Clin. Med., 91 (4), 710 –716 (1978). JLCMAK 0022-2143 Google Scholar


P. Granjean and J. Lintrup, “Sources of variation in fluorometry of zinc protoporphyrin in blood,” Scand. J. Work Environ. Health, 7 (4), 311 –312 (1981). SWEHDO 0355-3140 Google Scholar


R. F. Labbe, A. Dewanji and K. McLaughlin, “Observations on the zinc protoporphyrin/heme ratio in whole blood,” Clin. Chem., 45 (1), 146 –148 (1999). CLCHAU 0009-9147 Google Scholar


R. Gorodetsky et al., “Direct fluorometric determination of erythrocyte free and zinc protoporphyrins in health and disease,” Clin. Biochem., 18 (6), 362 –368 (1985). CLBIAS 0009-9120 Google Scholar


R. B. Schifman and P. R. Finley, “Measurement of near-normal concentrations of erythrocyte protoporphyrin with the hematofluorometer: influence of plasma on ‘front-surface illumination’ assay,” Clin. Chem., 27 (1), 153 –156 (1981). CLCHAU 0009-9147 Google Scholar


G. Hennig et al., “Bandwidth-variable tunable optical filter unit for illumination and spectral imaging systems using thin-film optical band-pass filters,” Rev. Sci. Instrum., 84 (4), 043113 (2013). RSINAK 0034-6748 Google Scholar


I. Pavlova et al., “Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer,” J. Biomed. Opt., 13 (6), 064012 (2008). JBOPFO 1083-3668 Google Scholar


CBTRUS, “CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2004-2007,” (2011) Google Scholar


M. L. Siker et al., “Age as an independent prognostic factor in patients with glioblastoma: a Radiation Therapy Oncology Group and American College of Surgeons National Cancer Data Base comparison,” J. Neurooncol., 104 (1), 351 –356 (2011). JNODD2 0167-594X Google Scholar


J. D. Voigt and M. Torchia, “Laser interstitial thermal therapy with and without MRI guidance for treatment of brain neoplasms: a systematic review of the literature,” Photonics Lasers Med., 3 (2), 77 (2014). PLMHAJ 2193-0643 Google Scholar


T. R. Patel and V. L. S. Chiang, “Laser interstitial thermal therapy for treatment of post-radiosurgery tumor recurrence and radiation necrosis,” Photonics Lasers Med., 3 (2), 95 (2014). PLMHAJ 2193-0643 Google Scholar


S. Missios et al., “Prognostic factors of overall survival after laser interstitial thermal therapy in patients with glioblastoma,” Photonics Lasers Med., 3 (2), 143 (2014). PLMHAJ 2193-0643 Google Scholar


W. Stummer, M. J. van den Bent and M. Westphal, “Cytoreductive surgery of glioblastoma as the key to successful adjuvant therapies: new arguments in an old discussion,” Acta Neurochir. (Wien), 153 (6), 1211 –1218 (2011). ACNUA5 0001-6268 Google Scholar


W. Stummer et al., “In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid,” J. Photochem. Photobiol. B, 45 (2–3), 160 –169 (1998). JPPBEG 1011-1344 Google Scholar


W. Stummer et al., “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” Lancet Oncol., 7 (5), 392 –401 (2006). LOANBN 1470-2045 Google Scholar


M. Kriegmair et al., “Fluorescence cystoscopy following intravesical instillation of 5-aminolevulinic acid: a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urol. Int., 55 (4), 190 –196 (1995). URINAC 0042-1138 Google Scholar


M. Kriegmair et al., “Transurethral resection and surveillance of bladder cancer supported by 5-aminolevulinic acid-induced fluorescence endoscopy,” Eur. Urol., 36 (5), 386 –392 (1999). EUURAV 0302-2838 Google Scholar


W. Stummer et al., “Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence,” Neurosurgery, 42 (3), 518525 –525516 (1998). NEQUEB Google Scholar


W. Stummer et al., “Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue,” Acta Neurochir. (Wien), 140 (10), 995 –1000 (1998). ACNUA5 0001-6268 Google Scholar


M. Loshchenov et al., “Endoscopic fluorescence visualization of 5-ALA photosensitized central nervous system tumors in the neural tissue transparency spectral range,” Photonics Lasers Med., 3 (2), 159 (2014). PLMHAJ 2193-0643 Google Scholar


W. Stummer et al., “Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients,” J. Neurosurg., 93 (6), 1003 –1013 (2000). JONSAC 0022-3085 Google Scholar


J. T. Liu, D. Meza and N. Sanai, “Trends in fluorescence image-guided surgery for gliomas,” Neurosurgery, 75 (1), 61 –71 (2014). NEQUEB Google Scholar


S. Eljamel et al., “Comparison of intraoperative fluorescence and MRI image guided neuronavigation in malignant brain tumours, a prospective controlled study,” Photodiagnosis Photodyn. Ther., 10 (4), 356 –361 (2013). PPTHBF 1572-1000 Google Scholar


S. Zhao et al., “Intraoperative fluorescence-guided resection of high-grade malignant gliomas using 5-aminolevulinic acid-induced porphyrins: a systematic review and meta-analysis of prospective studies,” PLoS One, 8 (5), e63682 (2013). 1932-6203 Google Scholar


G. Aldave et al., “Prognostic value of residual fluorescent tissue in glioblastoma patients after gross total resection in 5-aminolevulinic acid-guided surgery,” Neurosurgery, 72 (6), 915920 –920911 (2013). NEQUEB Google Scholar


W. Stummer et al., “5-aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging,” Neurosurgery, 74 (3), 310319 –319320 (2014). NEQUEB Google Scholar


K. Svanberg et al., “Clinical and technical aspects of photodynamic therapy: superficial and interstitial illumination in skin and prostate cancer,” Handbook of Biophotonics, 261 –287 Wiley-VCH, Weinheim, Germany (2012). Google Scholar


B. Olzowy et al., “Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid,” J. Neurosurg., 97 (4), 970 –976 (2002). JONSAC 0022-3085 Google Scholar


S. Ito et al., “Oedema formation in experimental photo-irradiation therapy of brain tumours using 5-ALA,” Acta Neurochir. (Wien), 147 (1), 5765 –65 (2005). ACNUA5 0001-6268 Google Scholar


P. Zelenkov et al., “Acute morphological sequelae of photodynamic therapy with 5-aminolevulinic acid in the C6 spheroid model,” J. Neurooncol., 82 (1), 49 –60 (2007). JNODD2 0167-594X Google Scholar


H. G. Stepp et al., “Fluorescence-guided resections and photodynamic therapy for malignant gliomas using 5-aminolevulinic acid,” Proc. SPIE, 5686 547 –557 (2005). PSISDG 0277-786X Google Scholar


Y. Lee and E. D. Baron, “Photodynamic therapy: current evidence and applications in dermatology,” Semin. Cutan. Med. Surg., 30 (4), 199 –209 (2011). SCMSFR 1085-5629 Google Scholar


M. S. Eljamel, C. Goodman and H. Moseley, “ALA and photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre phase III randomised controlled trial,” Lasers Med. Sci., 23 (4), 361 –367 (2008). LMSCEZ 1435-604X Google Scholar


L. Lilge and B. C. Wilson, “Photodynamic therapy of intracranial tissues: a preclinical comparative study of four different photosensitizers,” J. Clin. Laser Med. Surg., 16 (2), 81 –91 (1998). JCLSEO Google Scholar


. L. Cui et al., “Porphyrin-lipid assembled HDL-like nanovesicles for fluorescence imaging and PDT treatment of orthotopic brain glioma tumor,” in Biomedical Optics 2014, (2014). Google Scholar


S. L. Bisland et al., “Metronomic photodynamic therapy (mPDT) for intracranial neoplasm: physiological, biological, and dosimetry considerations,” Proc. SPIE, 5142 9 –17 (2003). PSISDG 0277-786X Google Scholar


S. K. Bisland et al., “Metronomic photodynamic therapy as a new paradigm for photodynamic therapy: rationale and preclinical evaluation of technical feasibility for treating malignant brain tumors,” Photochem. Photobiol., 80 (1), 22 –30 (2004). PHCBAP 0031-8655 Google Scholar


T. J. Beck et al., “Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5-aminolevulinic acid induced protoporphyrin IX,” Lasers Surg. Med., 39 (5), 386 –393 (2007). LSMEDI 0196-8092 Google Scholar


A. Johansson et al., “Interstitial photodynamic therapy of brain tumors,” IEEE J. Sel. Topics Quantum Electron., 16 (4), 841 –853 (2010). IJSQEN 1077-260X Google Scholar


H. Stepp et al., “ALA and malignant glioma: fluorescence-guided resection and photodynamic treatment,” J. Environ. Pathol. Toxicol. Oncol., 26 (2), 157 –164 (2007). JEPOEC 0731-8898 Google Scholar


W. Stummer et al., “Long-sustaining response in a patient with non-resectable, distant recurrence of glioblastoma multiforme treated by interstitial photodynamic therapy using 5-ALA: case report,” J. Neurooncol., 87 (1), 103 –109 (2008). JNODD2 0167-594X Google Scholar


A. Johansson et al., “Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis,” Lasers Surg. Med., 45 (4), 225 –234 (2013). LSMEDI 0196-8092 Google Scholar


B. Lai et al., “Characterization of a miniature integrating cylinder for absolute calibration of fluence rate probes for interstitial photodynamic therapy (IPDT),” Proc. SPIE, 7373 73731M (2009). PSISDG 0277-786X Google Scholar


A. Johansson et al., “ALA-mediated fluorescence-guided resection (FGR) and PDT of glioma,” Proc. SPIE, 7380 73801D (2009). PSISDG 0277-786X Google Scholar


W. Göbel et al., “Optical needle endoscope for safe and precise stereotactically guided biopsy sampling in neurosurgery,” Opt. Express, 20 (24), 26117 –26126 (2012). OPEXFF 1094-4087 Google Scholar


A. Johansson et al., “Protoporphyrin IX for photodynamic therapy of brain tumours,” Proc. SPIE, 7715 77151M (2010). PSISDG 0277-786X Google Scholar


G. Hennig, H. Stepp and A. Johansson, “Photobleaching-based method to individualize irradiation time during interstitial 5-aminolevulinic acid photodynamic therapy,” Photodiagnosis Photodyn. Ther., 8 (3), 275 –281 (2011). PPTHBF 1572-1000 Google Scholar


A. Rühm et al., “5-ALA based photodynamic management of glioblastoma,” Proc. SPIE, 8928 89280E (2014). PSISDG 0277-786X Google Scholar


R. Siegel et al., “Cancer statistics, 2014,” CA Cancer J. Clin., 64 (1), 9 –29 (2014). CAMCAM 0007-9235 Google Scholar


A. Jemal et al., “Global cancer statistics,” CA Cancer J. Clin., 61 (2), 69 –90 (2011). CAMCAM 0007-9235 Google Scholar


“GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012,” Google Scholar


J. D. Campbell and S. D. Ramsey, “The costs of treating breast cancer in the USA synthesis of published evidence,” Pharmacoeconomics, 27 (3), 199 –209 (2009). PARMEK Google Scholar


Z. Kim et al., “The basic facts of Korean breast cancer in 2011: results of a nationwide survey and breast cancer registry database,” J. Breast Cancer, 17 (2), 99 –106 (2014). IJBCEW 2090-3189 Google Scholar


“Breast cancer screening programs in 26 ICSN countries, 2012: organization, policies, and program reach,” Google Scholar


A. N. Freedman et al., “Cancer risk prediction models: a workshop on development, evaluation, and application,” JNCI, 97 (10), 715 –723 (2005). JJIND8 0198-0157 Google Scholar


B. Rosner and G. A. Colditz, “Nurses’ health study: log-incidence mathematical model of breast cancer incidence,” J. Natl. Cancer Inst., 88 (6), 359 –364 (1996). JNCIEQ Google Scholar


N. F. Boyd et al., “Mammographic density and breast cancer risk: current understanding and future prospects,” Breast Cancer Res., 13 (6), (2011). BCTRD6 Google Scholar


Z. Aitken et al., “Screen-film mammographic density and breast cancer risk: a comparison of the volumetric standard mammogram form and the interactive threshold measurement methods,” Cancer Epidemiol. Biomarkers Prev., 19 (2), 418 –428 (2010). CEBPE4 1055-9965 Google Scholar


E. J. Walter and L. Lilge, “Development of a modified transillumination breast spectroscopy (TiBS) system for population-wide screening,” Proc. SPIE, 7368 736820 (2009). PSISDG 0277-786X Google Scholar


A. H. Gharekhan et al., “Characterizing fluorescence spectral features of cancer, benign and normal human breast tissues through wavelet transform and singular value decomposition,” Proc. SPIE, 7373 73730O (2009). PSISDG 0277-786X Google Scholar


A. Poellinger, “Near-infrared imaging of breast cancer using optical contrast agents,” J. Biophotonics, 5 (11–12), 815 –826 (2012). JBOIBX 1864-063X Google Scholar


L. Scolaro et al., “A review of optical coherence tomography in breast cancer,” Photonics Lasers Med., 3 (3), 225 (2014). PLMHAJ 2193-0643 Google Scholar


P. Taroni et al., “Breast density assessment by means of time domain optical mammography at 635-1060 nm,” Proc. SPIE, 8088 80881E (2011). PSISDG 0277-786X Google Scholar


P. Taroni et al., “Optical identification of subjects at high risk for developing breast cancer,” Proc. SPIE, 8799 87990O (2013). PSISDG 0277-786X Google Scholar


K. M. Blackmore et al., “Estimation of mammographic density on an interval scale by transillumination breast spectroscopy,” J. Biomed. Opt., 13 (6), 8 (2008). JBOPFO 1083-3668 Google Scholar


K. Blyschak et al., “Classification of breast tissue density by optical transillumination spectroscopy: optical and physiological effects governing predictive value,” Med. Phys., 31 (6), 1398 –1414 (2004). MPHYA6 0094-2405 Google Scholar


J. A. Knight et al., “Optical spectroscopy of the breast in premenopausal women reveals tissue variation with changes in age and parity,” Med. Phys., 37 (2), 419 –426 (2010). MPHYA6 0094-2405 Google Scholar


N. F. Boyd et al., “Evidence that breast tissue stiffness is associated with risk of breast cancer,” Plos One, 9 (7), (2014). 1932-6203 Google Scholar


A. Pettersson et al., “Mammographic density phenotypes and risk of breast cancer: a meta-analysis,” J. Natl. Cancer Inst., 106 (5), (2014). JNCIEQ Google Scholar


O. M. Ginsburg, L. J. Martin and N. F. Boyd, “Mammographic density, lobular involution, and risk of breast cancer,” Br. J. Cancer, 99 (9), 1369 –1374 (2008). BJCAAI 0007-0920 Google Scholar


K. M. Blackmore, J. A. Knight and L. Lilge, “Association between transillumination breast spectroscopy and quantitative mammographic features of the breast,” Cancer Epidemiol. Biomarkers Prev., 17 (5), 1043 –1050 (2008). CEBPE4 1055-9965 Google Scholar


M. K. Simick and L. Lilge, “Optical transillumination spectroscopy to quantify parenchymal tissue density: an indicator for breast cancer risk,” Br. J. Radiol., 78 (935), 1009 –1017 (2005). BJRAAP 0007-1285 Google Scholar


T. J. Farrell, M. S. Patterson and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys., 19 (4), 879 –888 (1992). MPHYA6 0094-2405 Google Scholar


K. Blyschak et al., “Classification of breast tissue density by optical transillumination spectroscopy: optical and physiological effects governing predictive value,” in Applications of Photonic Technology 6: Closing the Gap between Theory, Development, and Application, 568 –579 (2003). Google Scholar


L. Lilge et al., “Optical transillumination spectroscopy as biomarker for breast tissue density and cancer risk,” Cancer Epidemiol. Biomarkers Prev., 13 (11), 1910S (2004). CEBPE4 1055-9965 Google Scholar


M. K. Simick, B. C. Wilson and L. D. Lilge, “Optical transillumination spectroscopy of breast tissue for cancer risk assessment,” Proc. SPIE, 4609 390 –397 (2002). Google Scholar


J. E. Gunther et al., “Predicting tumor response in breast cancer patients using diffuse optical tomography,” Proc. SPIE, 8799 87990P (2013). PSISDG 0277-786X Google Scholar


M. Alrubaiee et al., “Multi-wavelength diffusive optical tomography using independent component analysis and time reversal algorithms,” Proc. SPIE, 8088 80880Y (2011). PSISDG 0277-786X Google Scholar


I. Bargigia et al., “Time-resolved diffuse optical spectroscopy up to 1700 nm using a time-gated InGaAs/InP single-photon avalanche diode,” Proc. SPIE, 8090 80900U (2011). PSISDG 0277-786X Google Scholar


A. Pifferi et al., “Time-domain diffuse optical spectroscopy beyond 1100 nm: initial feasibility study,” Proc. SPIE, 8088 808817 (2011). PSISDG 0277-786X Google Scholar


F. Tellier et al., “Comparison of 2- and 4-wavelength methods for the optical detection of sentinel lymph node,” Proc. SPIE, 8092 80920L (2011). PSISDG 0277-786X Google Scholar


B. J. Tromberg et al., “Assessing the future of diffuse optical imaging technologies for breast cancer management,” Med. Phys., 35 (6), 2443 –2451 (2008). MPHYA6 0094-2405 Google Scholar


J. Wang et al., “Near-infrared tomography of breast cancer hemoglobin, water, lipid, and scattering using combined frequency domain and cw measurement,” Opt. Lett., 35 (1), 82 –84 (2010). OPLEDP 0146-9592 Google Scholar


C. Zhou et al., “Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy,” J. Biomed. Opt., 12 (5), 051903 (2007). JBOPFO 1083-3668 Google Scholar


Y. Lin, O. Nalcioglu and G. Gulsen, “Fiber bundle based fluorescence tomography system for human breast imaging,” Proc. SPIE, 7371 737108 (2009). PSISDG 0277-786X Google Scholar


V. Piron and J.-P. L’Huillier, “Resolution limits between objects embedded in breast-like slab using the optical frequency-domain method: a numerical approach,” Proc. SPIE, 8092 80920O (2011). PSISDG 0277-786X Google Scholar


M. Guven et al., “Diffuse optical tomography with a priori anatomical information,” Phys. Med. Biol., 50 (12), 2837 –2858 (2005). PHMBA7 0031-9155 Google Scholar


A. Li et al., “Optimal linear inverse solution with multiple priors in diffuse optical tomography,” Appl. Opt., 44 (10), 1948 –1956 (2005). APOPAI 0003-6935 Google Scholar


P. K. Yalavarthy et al., “Structural information within regularization matrices improves near infrared diffuse optical tomography,” Opt. Express, 15 (13), 8043 –8058 (2007). OPEXFF 1094-4087 Google Scholar


H. Soliman et al., “Functional imaging using diffuse optical spectroscopy of neoadjuvant chemotherapy response in women with locally advanced breast cancer,” Clin. Cancer Res., 16 (9), 2605 –2614 (2010). CCREF4 1078-0432 Google Scholar


M. Heijblom et al., “Breast imaging using the Twente Photoacoustic Mammoscope (PAM): new clinical measurements,” Proc. SPIE, 8087 80870N (2011). PSISDG 0277-786X Google Scholar


M. Heijblom et al., “Photoacoustic imaging of breast tumor vascularization: a comparison with MRI and histopathology,” Proc. SPIE, 8800 880004 (2013). PSISDG 0277-786X Google Scholar


T. Kitai et al., “Photoacoustic mammography: initial clinical results,” Breast Cancer, 21 (2), 146 –153 (2014). BCATDJ 0161-0112 Google Scholar


R. G. Pleijhuis et al., “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol., 16 (10), 2717 –2730 (2009). 1068-9265 Google Scholar


J. S. D. Mieog et al., “Image-guided tumor resection using real-time near-infrared fluorescence in a syngeneic rat model of primary breast cancer,” Breast Cancer Res. Treat., 128 (3), 679 –689 (2011). BCTRD6 Google Scholar


J. S. D. Mieog et al., “Novel intraoperative near-infrared fluorescence camera system for optical image-guided cancer surgery,” Mol. Imaging, 9 (4), 223 –231 (2010). MIOMBP 1535-3508 Google Scholar


B. E. Schaafsma et al., “The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery,” J. Surg. Oncol., 104 (3), 323 –332 (2011). JSONAU 0022-4790 Google Scholar


W. B. Guo et al., “Breast cancer sentinel lymph node mapping using near-infrared guided indocyanine green in comparison with blue dye,” Tumor Biol., 35 (4), 3073 –3078 (2014). TUMBEA 1010-4283 Google Scholar


N. Haj-Hosseini et al., “Fluorescence spectroscopy using indocyanine green for lymph node mapping,” Proc. SPIE, 8935 893504 (2014). PSISDG 0277-786X Google Scholar


F. P. R. Verbeek et al., “Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience,” Breast Cancer Res. Treat., 143 (2), 333 –342 (2014). BCTRD6 Google Scholar


L. Xiong et al., “Indocyanine green fluorescence-guided sentinel node biopsy: a meta-analysis on detection rate and diagnostic performance,” EJSO, 40 (7), 843 –849 (2014). 0748-7983 Google Scholar


Z. Huang, “A review of progress in clinical photodynamic therapy,” Technol. Cancer Res. Treat., 4 (3), 283 –293 (2005). TCRTBS 1533-0346 Google Scholar


J. D. Miller et al., “Photodynarnic therapy with the phthalocyanine photosensitizer Pc 4: the case experience with preclinical mechanistic and early clinical-translational studies,” Toxicol. Appl. Pharmacol., 224 (3), 290 –299 (2007). TXAPA9 0041-008X Google Scholar


K. H. Haraldsdottir et al., “Interstitial laser thermotherapy (ILT) of breast cancer,” EJSO, 34 (7), 739 –745 (2008). 0748-7983 Google Scholar


S. C. Jiang and X. X. Zhang, “Dynamic modeling of photothermal interactions for laser-induced interstitial thermotherapy: parameter sensitivity analysis,” Lasers Med. Sci., 20 (3–4), 122 –131 (2005). LMSCEZ 1435-604X Google Scholar


H. Choi and Z. Tovar-Spinoza, “MRI-guided laser interstitial thermal therapy of intracranial tumors and epilepsy: state-of-the-art review and a case study from pediatrics,” Photonics Lasers Med., 3 (2), 107 (2014). PLMHAJ 2193-0643 Google Scholar


D. S. Robinson et al., “Interstitial laser hyperthermia model development for minimally invasive therapy of breast carcinoma,” J. Am. Coll. Surg., 186 (3), 284 –292 (1998). JACSEX 1072-7515 Google Scholar


T. Schroder et al., “Percutaneous interstitial laser hyperthermia in clinical use,” Ann. Chir. Gynaecol., 83 (4), 286 –290 (1994). ACGYDJ 0355-9521 Google Scholar


K. G. Tranberg, “Laser tumor thermotherapy: is there a clinically relevant effect on the immune system?,” Proc. SPIE, 6087 60870B (2006). PSISDG 0277-786X Google Scholar


M. K. Akens et al., “Photodynamic therapy of vertebral metastases: evaluating tumor-to-neural tissue uptake of BPD-MA and ALA-PpIX in a murine model of metastatic human breast carcinoma,” Photochem. Photobiol., 83 (5), 1034 –1039 (2007). PHCBAP 0031-8655 Google Scholar


N. Batista and D. Liang, “A simple color separation technique for solar tissue photocoagulation,” Proc. SPIE, 8092 80921K (2011). PSISDG 0277-786X Google Scholar


C. W. Chang and W. R. Ries, “Surgical treatment of the inferior turbinate: new techniques,” Curr. Opin. Otolaryngol. Head Neck Surg., 12 (1), 53 –57 (2004). 1068-9508 Google Scholar


R. Mladina, R. Risavi and M. Subaric, “CO2 laser anterior turbinectomy in the treatment of non-allergic vasomotor rhinopathia. A prospective study upon 78 patients,” Rhinology, 29 (4), 267 –271 (1991). RNGYA8 Google Scholar


A. DeRowe et al., “Subjective comparison of Nd:YAG, diode, and CO2 lasers for endoscopically guided inferior turbinate reduction surgery,” Am. J. Rhinol., 12 (3), 209 –212 (1998). AJRHE5 Google Scholar


E. Serrano et al., “The holmium:YAG laser for treatment of inferior turbinate hypertrophy,” Rhinology, 36 (2), 77 –80 (1998). RNGYA8 Google Scholar


A. Leunig et al., “Ho:YAG laser treatment of hyperplastic inferior nasal turbinates,” Laryngoscope, 109 (10), 1690 –1695 (1999). LARYA8 0023-852X Google Scholar


P. Janda et al., “Laser treatment of hyperplastic inferior nasal turbinates: a review,” Lasers Surg. Med., 28 (5), 404 –413 (2001). LSMEDI 0196-8092 Google Scholar


R. Sroka et al., “Endonasal laser surgery with a new laser fiber guidance instrument,” Laryngoscope, 110 (2 Pt 1), 332 –334 (2000). LARYA8 0023-852X Google Scholar


M. Havel et al., “A double-blind, randomized, intra-individual controlled feasibility trial comparing the use of 1, 470 and 940 nm diode laser for the treatment of hyperplastic inferior nasal turbinates,” Lasers Surg. Med., 43 (9), 881 –886 (2011). LSMEDI 0196-8092 Google Scholar


R. Sroka et al., “Controlled feasibility trial comparing the use of 1470 nm and 940 nm diode laser for the treatment of hyperplastic inferior nasal turbinates,” Proc. SPIE, 8207 82072Y (2012). PSISDG 0277-786X Google Scholar


C. S. Betz et al., “Coagulative and ablative characteristics of a novel diode laser system (1470 nm) for endonasal applications,” Proc. SPIE, 6842 68421Z (2008). PSISDG 0277-786X Google Scholar


R. Sroka et al., “Clinical feasibility trial on 1940 nm Tm: fiber laser intervention of hyperplastic inferior nasal turbinates,” Photonics Lasers Med., 1 (3), 215 (2012). PLMHAJ 2193-0643 Google Scholar


P. Janda et al., “Comparison of thermal tissue effects induced by contact application of fiber guided laser systems,” Lasers Surg. Med., 33 (2), 93 –101 (2003). LSMEDI 0196-8092 Google Scholar


P. Janda et al., “Diode laser treatment of hyperplastic inferior nasal turbinates,” Lasers Surg. Med., 27 (2), 129 –139 (2000). LSMEDI 0196-8092 Google Scholar


J. Newman and V. Anand, “Applications of the diode laser in otolaryngology,” Ear Nose Throat J., 81 (12), 850 –851 (2002). EENTAQ 0014-5491 Google Scholar


D. Passali et al., “Treatment of inferior turbinate hypertrophy: a randomized clinical trial,” Ann. Otol. Rhinol. Laryngol., 112 (8), 683 –688 (2003). AORHA2 0003-4894 Google Scholar


S. D. Rejali et al., “Inferior turbinate reduction in children using holmium YAG laser—a clinical and histological study,” Lasers Surg. Med., 34 (4), 310 –314 (2004). LSMEDI 0196-8092 Google Scholar


R. Sroka et al., “Comparison of long term results after Ho:YAG and diode laser treatment of hyperplastic inferior nasal turbinates,” Lasers Surg. Med., 39 (4), 324 –331 (2007). LSMEDI 0196-8092 Google Scholar


R. Sroka et al., “Laser treatment of hyperplastic inferior nasal turbinates: 1 year follow up,” in Biomedical Topical Meeting, Google Scholar


P. Janda et al., “Comparison of laser induced effects on hyperplastic inferior nasal turbinates by means of scanning electron microscopy,” Lasers Surg. Med., 30 (1), 31 –39 (2002). LSMEDI 0196-8092 Google Scholar


R. Sroka et al., “Treatment of hyperplastic inferior nasal turbinates by means of a Ho:YAG laser,” Proc. SPIE, 3590 229 –232 (1999). PSISDG 0277-786X Google Scholar


C. J. Nease and G. A. Krempl, “Radiofrequency treatment of turbinate hypertrophy: a randomized, blinded, placebo-controlled clinical trial,” Otolaryngol. Head Neck Surg., 130 (3), 291 –299 (2004). AONSEJ 0886-4470 Google Scholar


M. Cavaliere, G. Mottola and M. Iemma, “Monopolar and bipolar radiofrequency thermal ablation of inferior turbinates: 20-month follow-up,” Otolaryngol. Head Neck Surg., 137 (2), 256 –263 (2007). AONSEJ 0886-4470 Google Scholar


N. D. Bhandarkar and T. L. Smith, “Outcomes of surgery for inferior turbinate hypertrophy,” Curr. Opin. Otolaryngol. Head Neck Surg., 18 (1), 49 –53 (2010). 1068-9508 Google Scholar


D. Willatt, “The evidence for reducing inferior turbinates,” Rhinology, 47 (3), 227 –236 (2009). RNGYA8 Google Scholar


P. P. Caffier et al., “Rhinitis medicamentosa: therapeutic effect of diode laser inferior turbinate reduction on nasal obstruction and decongestant abuse,” Am. J. Rhinol., 22 (4), 433 –439 (2008). AJRHE5 Google Scholar


G. F. Volk et al., “Prognostic value of anterior rhinomanometry in diode laser turbinoplasty,” Arch. Otolaryngol. Head Neck Surg., 136 (10), 1015 –1019 (2010). AONSEJ 0886-4470 Google Scholar


L. Navarro, R. J. Min and C. Bone, “Endovenous laser: a new minimally invasive method of treatment for varicose veins: preliminary observations using an 810 nm diode laser,” Dermatol. Surg., 27 (2), 117 –122 (2001). DESUFE 1076-0512 Google Scholar


R. J. Min et al., “Endovenous laser treatment of the incompetent greater saphenous vein,” J. Vasc. Interv. Radiol., 12 (10), 1167 –1171 (2001). JVIRE3 1051-0443 Google Scholar


W. S. Malskat et al., “Endovenous laser ablation (EVLA): a review of mechanisms, modeling outcomes, and issues for debate,” Lasers Med. Sci., 29 (2), 393 –403 (2014). LMSCEZ 1435-604X Google Scholar


W. S. Malskat et al., “Temperature profiles of 980- and 1, 470-nm endovenous laser ablation, endovenous radiofrequency ablation and endovenous steam ablation,” Lasers Med. Sci., 29 (2), 423 –429 (2014). LMSCEZ 1435-604X Google Scholar


A. B. Massaki et al., “Endoluminal laser delivery mode and wavelength effects on varicose veins in an ex vivo model,” Lasers Surg. Med., 45 (2), 123 –129 (2013). LSMEDI 0196-8092 Google Scholar


M. Heger et al., “Endovascular laser-tissue interactions and biological responses in relation to endovenous laser therapy,” Lasers Med. Sci., 29 (2), 405 –422 (2014). LMSCEZ 1435-604X Google Scholar


R. Sroka et al., “Ex-vivo investigations on endoluminal vein treatment procedures,” Proc. SPIE, 6424 64240M (2007). PSISDG 0277-786X Google Scholar


R. Sroka et al., “The ox-foot-model for investigating endoluminal thermal treatment modalities of varicosis vein diseases,” ALTEX, 29 (4), 403 –410 (2012). ALTCDD Google Scholar


R. Sroka et al., “Endovenous laser therapy—application studies and latest investigations,” J. Biophotonics, 3 (5–6), 269 –276 (2010). JBOIBX 1864-063X Google Scholar


R. Brar et al., “Surgical management of varicose veins: meta-analysis,” Vascular, 18 (4), 205 –220 (2010). VASCBO 1708-5381 Google Scholar


C. Carroll et al., “Systematic review, network meta-analysis and exploratory cost-effectiveness model of randomized trials of minimally invasive techniques versus surgery for varicose veins,” Br. J. Surg., 101 (9), 1040 –1052 (2014). BJSUAM 0007-1323 Google Scholar


. N. P. Lynch, M. Clarke and G. J. Fulton, “Surgical management of great saphenous vein varicose veins: a meta-analysis,” Vascular, (2014). VASCBO 1708-5381 Google Scholar


C. Nesbitt et al., “Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus open surgery for great saphenous vein varices,” Cochrane Database Syst. Rev., 7 CD005624 (2014). 1469-493X Google Scholar


Y. Pan et al., “Comparison of endovenous laser ablation and high ligation and stripping for varicose vein treatment: a meta-analysis,” Phlebology, 29 (2), 109 –119 (2014). PHLEEF Google Scholar


B. Siribumrungwong et al., “A systematic review and meta-analysis of randomised controlled trials comparing endovenous ablation and surgical intervention in patients with varicose vein,” Eur. J. Vasc. Endovasc. Surg., 44 (2), 214 –223 (2012). 1078-5884 Google Scholar


R. van den Bos et al., “Endovenous therapies of lower extremity varicosities: a meta-analysis,” J. Vasc. Surg., 49 (1), 230 –239 (2009). 0741-5214 Google Scholar


R. Sroka et al., “Endovenous laser application. Strategies to improve endoluminal energy application,” Phlebologie, 42 (3), 121 –129 (2013). 0939-978X Google Scholar


C. M. Fan and R. Rox-Anderson, “Endovenous laser ablation: mechanism of action,” Phlebology, 23 (5), 206 –213 (2008). PHLEEF Google Scholar


M. E. Vuylsteke and S. R. Mordon, “Endovenous laser ablation: a review of mechanisms of action,” Ann. Vasc. Surg., 26 (3), 424 –433 (2012). AVSUEV 0890-5096 Google Scholar


M. J. van Gemert et al., “Comment to Vuylsteke ME and Mordon SR. Endovenous laser ablation: a review of mechanisms of action. Ann Vasc Surg 2012;26:424-33,” Ann. Vasc. Surg., 26 (6), 881 –883 (2012). AVSUEV 0890-5096 Google Scholar


T. M. Proebstle, T. Moehler and S. Herdemann, “Reduced recanalization rates of the great saphenous vein after endovenous laser treatment with increased energy dosing: definition of a threshold for the endovenous fluence equivalent,” J. Vasc. Surg., 44 (4), 834 –839 (2006). 0741-5214 Google Scholar


T. Stokbroekx et al., “Commonly used fiber tips in endovenous laser ablation (EVLA): an analysis of technical differences,” Lasers Med. Sci., 29 (2), 501 –507 (2014). LMSCEZ 1435-604X Google Scholar


S. R. Mordon, B. Wassmer and J. Zemmouri, “Mathematical modeling of 980-nm and 1320-nm endovenous laser treatment,” Lasers Surg. Med., 39 (3), 256 –265 (2007). LSMEDI 0196-8092 Google Scholar


S. R. Mordon, B. Wassmer and J. Zemmouri, “Mathematical modeling of endovenous laser treatment (ELT),” Biomed. Eng. Online, 5 26 (2006). 1475-925X Google Scholar


P. W. van Ruijven et al., “Optical-thermal mathematical model for endovenous laser ablation of varicose veins,” Lasers Med. Sci., 29 (2), 431 –439 (2014). LMSCEZ 1435-604X Google Scholar


A. A. Poluektova et al., “Some controversies in endovenous laser ablation of varicose veins addressed by optical-thermal mathematical modeling,” Lasers Med. Sci., 29 (2), 441 –452 (2014). LMSCEZ 1435-604X Google Scholar


V. P. Minaev et al., “Endovenous laser treatment (EVLT) of safernous vein reflux with 1.56 μm laser,” Proc. SPIE, 7373 73731D (2009). PSISDG 0277-786X Google Scholar


C. G. Schmedt et al., “Evaluation of endovenous radiofrequency ablation and laser therapy with endoluminal optical coherence tomography in an ex vivo model,” J. Vasc. Surg., 45 (5), 1047 –1058 (2007). 0741-5214 Google Scholar


C. G. Schmedt et al., “Investigation on radiofrequency and laser (980 nm) effects after endoluminal treatment of saphenous vein insufficiency in an ex-vivo model,” Eur. J. Vasc. Endovasc. Surg., 32 (3), 318 –325 (2006). 1078-5884 Google Scholar


N. Bosschaart et al., “A literature review and novel theoretical approach on the optical properties of whole blood,” Lasers Med. Sci., 29 (2), 453 –479 (2014). LMSCEZ 1435-604X Google Scholar


R. Sroka et al., “Ex-vivo investigation of endoluminal vein treatment by means of radiofrequency and laser irradiation,” Med. Laser Appl., 21 (1), 15 –22 (2006). 1615-1615 Google Scholar


N. Topaloglu et al., “Comparison of 980-nm and 1070-nm in endovenous laser treatment (EVLT),” Proc. SPIE, 7373 73731S (2009). PSISDG 0277-786X Google Scholar


R. Baumgartner et al., “Tissue laser ablation process and device,” (1998). Google Scholar


F. Pannier, E. Rabe and U. Maurins, “First results with a new 1470-nm diode laser for endovenous ablation of incompetent saphenous veins,” Phlebology, 24 (1), 26 –30 (2009). PHLEEF Google Scholar


U. Maurins, E. Rabe and F. Pannier, “Does laser power influence the results of endovenous laser ablation (EVLA) of incompetent saphenous veins with the 1470-nm diode laser? A prospective randomized study comparing 15 and 25 W,” Int. Angiol., 28 (1), 32 –37 (2009). INANEK 0392-9590 Google Scholar


S. Doganci and U. Demirkilic, “Comparison of 980 nm laser and bare-tip fibre with 1470 nm laser and radial fibre in the treatment of great saphenous vein varicosities: a prospective randomised clinical trial,” Eur. J. Vasc. Endovasc. Surg., 40 (2), 254 –259 (2010). 1078-5884 Google Scholar


F. Pannier et al., “Endovenous laser ablation of great saphenous veins using a 1470 nm diode laser and the radial fibre: follow-up after six months,” Phlebology, 26 (1), 35 –39 (2011). PHLEEF Google Scholar


T. Schwarz et al., “Endovenous laser ablation of varicose veins with the 1470-nm diode laser,” J. Vasc. Surg., 51 (6), 1474 –1478 (2010). 0741-5214 Google Scholar


M. Vuylsteke et al., “Endovenous laser treatment: is there a clinical difference between using a 1500 nm and a 980 nm diode laser? A multicenter randomised clinical trial,” Int. Angiol., 30 (4), 327 –334 (2011). INANEK 0392-9590 Google Scholar


M. Mozafar et al., “Endovenous laser ablation of the great saphenous vein versus high ligation: long-term results,” Lasers Med. Sci., 29 (2), 765 –771 (2014). LMSCEZ 1435-604X Google Scholar


R. R. van den Bos and T. M. Proebstle, “The state of the art of endothermal ablation,” Lasers Med. Sci., 29 (2), 387 –392 (2014). LMSCEZ 1435-604X Google Scholar


E. von Hodenberg et al., “Endovenous laser ablation of varicose veins with the 1470 nm diode laser using a radial fiber: 1-year follow-up,” Phlebology, 30 (2), 86 –90 (2015). PHLEEF Google Scholar


P. Gloviczki et al., “The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum,” J. Vasc. Surg., 53 (5 Suppl), 2S –48S (2011). 0741-5214 Google Scholar


Varicose Veins in the Legs. The Diagnosis and Management of Varicose Veins, (2013). Google Scholar


K. Rass et al., “Comparable effectiveness of endovenous laser ablation and high ligation with stripping of the great saphenous vein: two-year results of a randomized clinical trial (RELACS study),” Arch. Dermatol, 148 (1), 49 –58 (2012). ARDEAC 0003-987X Google Scholar


J. P. Tesmann et al., “Radiofrequency induced thermotherapy (RFITT) of varicose veins compared to endovenous laser treatment (EVLT): a non-randomized prospective study concentrating on occlusion rates, side-effects and clinical outcome,” Eur. J. Dermatol., 21 (6), 945 –951 (2011). EJDEE4 1167-1122 Google Scholar


L. H. Rasmussen et al., “Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins,” Br. J. Surg., 98 (8), 1079 –1087 (2011). BJSUAM 0007-1323 Google Scholar


B. C. Disselhoff et al., “Five-year results of a randomized clinical trial comparing endovenous laser ablation with cryostripping for great saphenous varicose veins,” Br. J. Surg., 98 (8), 1107 –1111 (2011). BJSUAM 0007-1323 Google Scholar


B. C. Disselhoff et al., “Five-year results of a randomised clinical trial of endovenous laser ablation of the great saphenous vein with and without ligation of the saphenofemoral junction,” Eur. J. Vasc. Endovasc. Surg., 41 (5), 685 –690 (2011). 1078-5884 Google Scholar


T. Luebke and J. Brunkwall, “Systematic review and meta-analysis of endovenous radiofrequency obliteration, endovenous laser therapy, and foam sclerotherapy for primary varicosis,” J. Cardiovasc. Surg. (Torino), 49 (2), 213 –233 (2008). JCVSA2 0021-9509 Google Scholar


T. Luebke et al., “Meta-analysis of endovenous radiofrequency obliteration of the great saphenous vein in primary varicosis,” J. Endovasc. Ther., 15 (2), 213 –223 (2008). Google Scholar


R. Sroka et al., “Endovenous laser application. possibilities of online monitoring,” Phlebologie, 42 (3), 131 –138 (2013). 0939-978X Google Scholar


Ronald Sroka received his physics diploma at the Georg-August-University of Göttingen, Germany, and his PhD degree in the field of photodynamic therapy at the University of Munich, Germany. His research is focused on various aspects of photodynamic therapy and on thermal laser applications in a variety of clinical disciplines. Since 2010, he has been the head of the Laser-Forschungslabor in the LIFE Center at the hospital of the University of Munich.

Herbert Stepp received his diploma in physics in 1984 and has worked since then on photodynamic procedures. He obtained his PhD degree at the medical faculty of the University of Munich and became a research group leader at the LIFE Center in 1993. His research focuses on optics-based methods for the detection of cancer and other disorders. His research on 5-aminolevulinic acid based fluorescence techniques contributed to the approvals of fluorescence cystoscopy and fluorescence-guided resection of malignant glioma.

Georg Hennig is a physicist at the Laser-Forschungslabor, Klinikum der Universität München. He received his PhD degree in the field of fluorescence diagnostics. He currently focuses on medical device development and evaluation.

Gary M. Brittenham is the James A. Wolff professor of pediatrics and professor of medicine at the Columbia University College of Physicians and Surgeons. His research interests involve basic and clinical research in disorders of the red blood cell and of iron metabolism. His laboratory has helped develop noninvasive means for the measurement of tissue iron using magnetic susceptometry and magnetic resonance methods.

Adrian Rühm received his diploma in physics in 1993 and his PhD degree in 1998, at the Universities of München and Wuppertal, Germany, respectively. He worked in materials science with x-rays and neutrons in Stuttgart and Garching, Germany, and in Chicago, United States. In 2011, he joined the Laser-Forschungslabor in München, Germany, to conduct research in the field of biophotonics for medical applications. His current research activities are focused on photodynamic therapy and in vivo photodiagnosis.

Lothar Lilge completed his initial training at the University of Frankfurt, Germany, in the group of Dr. Hillenkamp. He worked at the Wellman Laboratory of Photomedicine in Boston, United States, and as a postdoc at McMaster University in Hamilton, Canada. His main research thrust pertains to photodynamic therapy in oncology, diffuse reflectance for breast cancer risk assessment, and microfluidics for single-cell analysis. Currently, he is a senior scientist at the Princess Margaret Cancer Centre and professor at the University of Toronto.

© 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) 1083-3668/2015/$25.00 © 2015 SPIE
Ronald Sroka, Herbert Stepp, Georg Hennig, Gary M. Brittenham, Adrian Rühm, and Lothar Lilge "Medical laser application: translation into the clinics," Journal of Biomedical Optics 20(6), 061110 (16 June 2015).
Published: 16 June 2015

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