Oxygen is a vital component in wound healing; however, microvascular dysfunction can impact the wound healing process by restricting the flow of oxygen to the site. Patients afflicted with cardiometabolic diseases, such as diabetes, are predisposed towards microvascular insufficiencies and may experience stagnated healing of injured tissues. In past literature Vascular Occlusion Tests (VOTs), coupled with NIRS-based imaging approaches, have been applies with the goal of assessing oxygenated flow to a site; either as dynamic, point-based, measurements or wide-area measurements at discrete timepoints. Breath-holding (BH), as a stimulus, holds potential to induce oxygenated flow changes without the need for additional equipment and the potential discomfort associated with vascular occlusion. In this study, end-exhalation breath-holding was applied on normal subjects. Each subject was imaged via an in-house build Near InfraRed Optical Scanner (NIROS) to acquire continuous spatio-temporal maps of effective hemoglobinbased parameters. Average trendlines of the effective parameters (via oxy- (ΔHbO), deoxy- (ΔHbR), total hemoglobin (ΔHbT), and oxygen saturation (ΔStO2)) were extracted. In addition, a Pearson’s correlation-based approach was applied to obtain correlation maps in terms of the oxygenated flow. Results indicated that statistically significant changes in the oxygenated flow was observed between the BH phase and post-BH phase, with correlation maps indicating regions of positively correlated flow in control subjects. Breath-holding holds potential as a technique to assess oxygenated flow changes and the extent of change between a given site to its surroundings in disease models, as currently assessed in diabetic foot ulcers and radiation dermatitis applications.
Proc. SPIE. 11639, Optical Tomography and Spectroscopy of Tissue XIV
KEYWORDS: Signal to noise ratio, Optical imaging, Near infrared, Principal component analysis, Tissues, Imaging systems, Cameras, Sensors, Interference (communication), Signal detection
Near-infrared (NIR) optical imaging systems are developed in an effort to maximize signal to noise ratio (SNR). Recently, a SmartPhone Oxygenation Tool (SPOT) was developed to obtain tissue oxygenation maps from dual-wavelength NIR images. Herein, several noise removal techniques are implemented to the NIR data obtained with SPOT in an effort to improve SNR for low-cost effective imaging of tissue oxygenation maps. NIR and oxygenation changes obtained from standard occlusion studies on normal subjects are compared with and without the noise removal techniques and the improvement in SNR is assessed.
Complications of the diabetic foot proliferate from ischemic and/or neuropathic conditions in the form of excess tissue build-up or callus. Plantar calluses are thick and soft and form as a result of neuropathy at the toe apices and metatarsals head and/or toe tips. Neuro-ischemic calluses appear thin, hard, dry and/or glassy and typically form at the borders of the feet and/or on main weight bearing areas. It is standard practice for the clinician to remove this excess tissue to reduce pressure in the diabetic foot which reduces the risk of ulceration. The dead tissue layers are removed in a surgical process known as scalpel debridement, or chiropody. It is not uncommon for a clinician to encounter a buried wound in the process of scalpel debridement. However, the process itself is not straightforward in that the extent of debridement is not measurable between clinicians. The debridement process removes tissue up to the epidermal-dermal junction, which may be difficult to identify for an inexperienced clinician. In an effort to measure the effect of scalpel debridement, near infrared (NIR) imaging was applied in an IRB study between Florida International University and Dr. Mohan’s Diabetes Specialties Centre in Chennai, India. Subjects were assessed before and after the debridement procedure. NIR images at multiple wavelengths were obtained before and after debridement to estimate changes in tissue oxygenation in the callus and surrounding peri-callus regions. A method to analyze the significance of oxygenation change occurring both overall and within sub-quadrants of the callus is conducted to assess the effect of debridement. Measuring changes in tissue oxygenation may potentially be used in future clinical applications to improve the debridement process and reduce the risk of ulceration.
Proc. SPIE. 11618, Photonics in Dermatology and Plastic Surgery 2021
KEYWORDS: Chest, Cancer, Breast cancer, Tissues, Skin, Oxygen, Radiotherapy, Skin cancer, Medical imaging, Tissue optics, Biomedical optics and medical imaging
The American Cancer Society has estimated that a total of 1.8 million new cancer cases will arise in 2020, 15% percent of which are breast cancer. Radiation therapy (RT) is widely used post mastectomy or lumpectomy as a method of avoiding recurrence of disease in affected regions. Photon and proton therapy are among the main forms of RT currently applied to breast cancer patients. The effectiveness of photon vs proton therapy has been studied in various cancer models from differences in subjective clinical grading of radiation dermatitis (RD), a common side effect of RT. Herein, an objective physiological imaging approach using near-infrared optical techniques is implemented to quantitatively differentiate the effectiveness of proton vs photon therapy in breast cancer subjects undergoing RT. A 6-8 week longitudinal pilot study (WIRB approved) was carried out on 10 breast cancer subjects undergoing RT at Miami Cancer Institute (MCI). The chest wall, axilla, and lower neck were imaged on the irradiated and the non-irradiated (contralateral) sides of the torso to measure for tissue oxygenation changes. From preliminary analysis, it was observed that were distinct differences in tissue oxygenation and RD in the irradiated regions when compared to their contralateral nonirradiated tissue (reference). Changes in tissue oxygenation and skin toxicity (i.e. RD clinical grading) were more localized and less severe in subjects receiving proton therapy compared to photon therapy. Quantitative comparison of oxygenation changes and its correlation to the skin toxicity levels in photon vs proton therapy treated breast cancer subjects is currently carried out.
Major challenges in diabetic foot ulcer (DFU) treatment include compliance and routine clinical visits to facilitate healing. Virtual Medicine (VM) can greatly impact DFU wound care management with tools for remote patient monitoring (RPM). Herein, a novel low-cost smartphone-based imaging device was developed to provide physiological (in terms of tissue oxygenation) and visual measurements of DFUs. Quantitative changes in tissue oxygenation between the wound and peri-wound in DFUs are obtained using SPOT device in an IRB approved pilot study. On a long-term, SPOT has potential to offer a low-cost alternative for VM and RPM in DFU wound care management.
According to the American Cancer Society, it is projected that 1.8 million new cancer cases will arise. Of these new cases, 15% are expected to be Breast Cancer related. For many subjects undergoing radiation therapy (RT), radiation dermatitis (RD) is an unavoidable adverse reaction to necessary treatment. As much as 95% of RT subjects will experience RD during or after their treatment plan which can range from mild erythema to full necrosis of the treated tissue. Further complicating matters, the standard assessment approach for RD, the Common Terminology Criteria for Adverse Events (CTCAE), is subjective and relies on the treating clinician’s visual assessment. Assessment of oxygenated blood flow changes holds potential as a means of assessing the severity of RD. In this study, spatial-temporal changes of tissue oxygenation, via a breath-hold paradigm, were monitored in breast cancer subjects across weeks of RT using a near infrared imaging approach. Subjects were imaged dynamically to acquire 2D spatial-temporal maps of tissue oxygenation. A Pearson’s correlation-based approach was applied to spatial-temporal oxygenation maps to determine the extent of symmetry or asymmetry in oxygenated blood flow patterns. Current results indicate that the oxygenated blood flow in tissue regions neighboring the irradiated site are affected by radiation dermatitis. These results are significant as they infer that RT induces altered oxygenated blood flow that could potentially be correlated to RD severity, apart from static tissue oxygenation measurements.
Near-infrared (NIR) spectroscopic imaging of wounds has been performed by past researchers to obtain tissue oxygenation at discrete point locations. We had developed a near-infrared optical scanner (NIROS) that performs noncontact NIR spectroscopic (NIRS) imaging to provide 2D tissue oxygenation maps of the entire wounds. Regions of changed oxygenation have to be demarcated and registered with respect to visual white light images of the wound. Herein, a semi-automatic image segmentation and co-registration approach using machine learning has been developed to differentiate regions of changed tissue oxygenation. A registration technique was applied using a transformation matrix approach using specific markers across the white light image and the NIR images (or tissue oxygenation maps). This allowed for physiological changes observed from hemodynamic changes to be observed in the RGB white light image as well. Semi-automated segmentation techniques employing graph cuts algorithms was implemented to demarcate the 2D tissue oxygenation maps depicting regions of increased or decreased oxygenation and further coregistered onto the white light images. The developed registration technique was validated via phantom studies (both flat and curved phantoms) and in-vivo studies on controls, demonstrating an accuracy >97%. The technique was further implemented on wounds (here, diabetic foot ulcers) across weeks of treatment. Regions of decreased oxygenation were demarcated, and its area estimated and co-registered in comparison to the clinically demarcated wound area. Future work involves the development of automated machine learning approaches of image analysis for clinicians to obtain real-time co-registered clinical and subclinical assessments of the wound.
Diabetic Foot Ulcers (DFUs) are responsible for 20% of diabetic-related hospitalization and 85% of diabetes related amputations. In DFUs the primary factor affecting healing is an adequate oxygen supply to the wound. However, the gold standard approach for assessing DFUs is by evaluating the reduction of wound size over a four-week period. In this study, we investigate the potential of altered breathing patterns as a technique to assess localized oxygenated perfusion in DFUs as a measure of healing potential. A continuous wave (CW), non-contact, near infrared optical scanner (NIROS) was used to conduct NIR based spectroscopic imaging at dual discrete wavelengths (729nm and 799nm) on DFUs with 7mW of maximum optical power. Subjects were imaged at discrete time points and dynamically utilizing an altered breathing paradigm (i.e. breath-hold) to measure the relative oxy- (ΔHbO) and deoxyhemoglobin (ΔHbR) changes in normal and DFU scenarios. Results show that in normal individuals, ΔHbO/ΔHbR changes at all points of the foot because of altered breathing patterns are synchronous; whereas in the DFU scenario changes in hemodynamic parameters are asynchronous. This indicates that under normal circumstances, oxygenated perfusion changes are consistent and uniform at all points of the foot as opposed to the DFU scenario’s inconsistent oxygenated perfusion. Altered breathing paradigms may serve as a useful tool in assessing localized sub-surface oxygenated perfusion in regions around the wound, and help clinicians better cater the treatment process.
Smartphone based wound image analysis approach has been recently developed to capture high resolution digital images of the wound and determine the wound size via image segmentation algorithms. Smartphone based technology has also been developed to obtain spectroscopic information at discrete point locations for brain imaging applications. Herein, we developed a low-cost smartphone based near-infrared (NIR) imaging device (between 650-1000 nm) that can measure tissue oxygenation in order to analyze wound healing status. Oxygen supply to ulcers is a key limiting factor for successful healing, and hence changes in tissue oxygenation are a precursor to visual changes in the wound. The use of multi-wavelength near-infrared light allows subcutaneous mapping of oxy- and deoxy-hemoglobin changes (or in turn tissue oxygenation changes). Validation studies were performed in controls to demonstrate changes in oxygenation (from diffuse reflectance changes) in response to venous occlusion. Currently, studies on diabetic foot ulcers is carried out using the cell phone-based imaging tool to obtain sub-surface tissue oxygenation maps of the wound and its surrounding. Smartphone based assessment of wounds will assist clinicians and nurses in any clinical in-house setting including low resource settings. In future, patients with chronic wounds can also actively participate (and comply) in their treatment process.
Lower extremity ulcers are one of the most common complications that not only affect many people around the world but also have huge impact on economy since a large amount of resources are spent for treatment and prevention of the diseases. Clinical studies have shown that reduction in the wound size of 40% within 4 weeks is an acceptable progress in the healing process. Quantification of the wound size plays a crucial role in assessing the extent of healing and determining the treatment process. To date, wound healing is visually inspected and the wound size is measured from surface images. The extent of wound healing internally may vary from the surface. A near-infrared (NIR) optical imaging approach has been developed for non-contact imaging of wounds internally and differentiating healing from non-healing wounds. Herein, quantitative wound size measurements from NIR and white light images are estimated using a graph cuts and region growing image segmentation algorithms. The extent of the wound healing from NIR imaging of lower extremity ulcers in diabetic subjects are quantified and compared across NIR and white light images. NIR imaging and wound size measurements can play a significant role in potentially predicting the extent of internal healing, thus allowing better treatment plans when implemented for periodic imaging in future.
Proc. SPIE. 9699, Optics and Biophotonics in Low-Resource Settings II
KEYWORDS: Optical imaging, Near infrared, MATLAB, Real time imaging, Wound healing, Image processing, Optical inspection, Data processing, Optical scanning, Absorption
Lower extremity ulcers are devastating complications that are still un-recognized. To date, clinicians employ visual inspection of the wound site during its standard 4-week of healing process via monitoring of surface granulation. A novel ultra-portable near-infrared optical scanner (NIROS) has been developed at the Optical Imaging Laboratory that can perform non-contact 2D area imaging of the wound site. From preliminary studies it was observed that the nonhealing wounds had a greater absorption contrast with respect to the normal site, unlike in the healing wounds. Currently, non-contact near-infrared (NIR) imaging studies were carried out on 22 lower extremity wounds at two podiatric clinics, and the sensitivity and specificity of the scanner evaluated. A quantitative optical biometric was developed that differentiates healing from non-healing wounds, based on the threshold values obtained during ROC analysis. In addition, optical images of the wound obtained from weekly imaging studies are also assessed to determine the ability of the device to predict wound healing consistently on a periodic basis. This can potentially impact early intervention in the treatment of lower extremity ulcers when an objective and quantitative wound healing approach is developed. Lastly, the incorporation of MATLAB graphical user interface (GUI) to automate the process of image acquisition, image processing and image analysis realizes the potential of NIROS to perform non-contact and real-time imaging on lower extremity wounds.
Diabetic foot ulcer is the most devastating complication of diabetes that is still un-recognized. The treatment costs of these ulcers are very high to eventually save the leg/foot from amputation. To date, clinicians employ visual inspection of the wound site during its standard 4-week of healing process via monitoring of surface granulation. There is a need to develop on-site, low-cost imaging tools that can monitor the wound healing process periodically during the standard 4-week treatment process. A novel ultra-portable near-infrared optical scanner (NIROS) has been developed at the Optical Imaging Laboratory that can perform non-contact 2D area imaging of the wound site. Non-contact optical imaging studies were carried on diabetic subjects with foot ulcers (at Somesh Diabetic Foot Clinic, India) that were of healing and non-healing nature. A 710 nm LED source and a compact NIR sensitive camera were employed during non-contact imaging of the diabetic foot in order to obtain the near-infrared absorption images. From these preliminary studies it was observed that the non-healing wounds had a greater absorption contrast with respect to the normal site, unlike in the healing wounds. Demonstrating the ability of NIROS to differentiate healing vs. non-healing wounds in diabetic subjects can potentially impact early intervention in the treatment of diabetic foot ulcers.
Non-contact based near-infrared (NIR) optical imaging devices are developed for non-invasive imaging of deep tissues in various clinical applications. Most of these devices focus on obtaining the spatial information for anatomical co-registration of blood vessels as in sub-surface vein localization applications. In the current study, the anatomical co-registration of blood vessels based on spatio-temporal features was performed using NIR optical imaging without the use of external contrast agents. A 710 nm LED source and a compact CCD camera system were employed during simple cuff (0 to 60 mmHg) experiment in order to acquire the dynamic NIR data from the dorsum of a hand. The spatio-temporal features of dynamic NIR data were extracted from the cuff experimental study to localize vessel according to blood dynamics. The blood vessels shape is currently reconstructed from the dynamic data based on spatio-temporal features. Demonstrating the spatio-temporal feature of blood dynamic imaging using a portable non-contact NIR imaging device without external contrast agents is significant for applications such as peripheral vascular diseases.
A novel Gen-2 hand-held optical imager was developed with capabilities to contour to different tissue curvatures, perform simultaneous illumination and detection and imager large tissue surfaces. Experimental studies using cubical phantoms demonstrated that the imager can detect targets up to 2.5 cm and 5 cm deep via reflectance and transmission measurements, respectively. The target was also localized as regions of high absorption during multi-scan imaging of curved breast phantoms via both reflectance and transmission modes. Preliminary in-vivo breast imaging demonstrated that the target can be detected via varying the pressure applied during imaging, as observed from reflectance-based imaging studies on healthy adults with superficially placed target(s) in the intra-mammary fold.
Proc. SPIE. 8578, Optical Tomography and Spectroscopy of Tissue X
KEYWORDS: Target detection, 3D acquisition, Imaging systems, Sensors, Luminescence, Image resolution, Tomography, 3D metrology, Signal detection, 3D image processing
A Gen-2 hand-held optical imager has been developed capable of 2D surface imaging and 3D tomography. In the current work, the capability of the imager to resolve two closely placed targets is assessed via 2D and 3D tomographic studies. Resolution studies have been carried out under various experimental conditions using slab phantoms. Preliminary 2D surface images of reflected measurements have demonstrated the ability of the system to resolve 0.95cm diameter targets placed 0.5cm apart at 2cm depth. Three dimensional tomography reconstructions are currently performed to assess the resolution capacity under different experimental conditions.
Near-infrared (NIR) optical imaging modality is one of the widely used medical imaging techniques for breast cancer
imaging, functional brain mapping, and many other applications. However, conventional NIR imaging systems are
bulky and expensive, thereby limiting their accelerated clinical translation. Herein a new compact (6 × 7 × 12 cm3),
cost-effective, and wide-field NIR scanner has been developed towards contact as well as no-contact based real-time
imaging in both reflectance and transmission mode. The scanner mainly consists of an NIR source light (between 700-
900 nm), an NIR sensitive CCD camera, and a custom-developed image acquisition and processing software to image an
area of 12 cm2. Phantom experiments have been conducted to estimate the feasibility of diffuse optical imaging by using
Indian-Ink as absorption-based contrast agents. As a result, the developed NIR system measured the light intensity
change in absorption-contrasted target up to 4 cm depth under transillumination mode. Preliminary in-vivo studies
demonstrated the feasibility of real-time monitoring of blood flow changes. Currently, extensive in-vivo studies are
carried out using the ultra-portable NIR scanner in order to assess the potential of the imager towards breast imaging..
Proc. SPIE. 8565, Photonic Therapeutics and Diagnostics IX
KEYWORDS: Sensors, Linear filtering, Kinematics, Semiconductor lasers, Data acquisition, Signal processing, Absorbance, Near infrared spectroscopy, Neuroimaging, Brain
Cerebral palsy (CP) is a term that describes a group of motor impairment syndromes secondary to genetic and/or
acquired disorders of the developing brain. In the current study, NIRS and motion capture were used simultaneously to correlate the brain’s planning and execution activity during and with arm movement in healthy individual. The prefrontal region of the brain is non-invasively imaged using a custom built continuous-wave based near infrared spectroscopy (NIRS) system. The kinematics of the arm movement during the studies is recorded using an infrared based motion capture system, Qualisys. During the study, the subjects (over 18 years) performed 30 sec of arm movement followed by 30 sec rest for 5 times, both with their dominant and non-dominant arm. The optical signal acquired from NIRS system was processed to elucidate the activation and lateralization in the prefrontal region of participants. The preliminary results show difference, in terms of change in optical response, between task and rest in healthy adults. Currently simultaneous NIRS imaging and kinematics data are acquired in healthy individual and individual with CP in order to correlate brain activity to arm movement in real-time. The study has significant implication in elucidating the evolution in the functional activity of the brain as the physical movement of the arm evolves using NIRS. Hence the study has potential in augmenting the designing of training and hence rehabilitation regime for individuals with CP via kinematic monitoring and imaging brain activity.
Hand-held optical imagers are developed by various researchers towards reflectance-based spectroscopic imaging of breast cancer. Recently, a Gen-1 handheld optical imager was developed with capabilities to perform two-dimensional (2-D) spectroscopic as well as three-dimensional (3-D) tomographic imaging studies. However, the imager was bulky with poor surface contact ( ∼ 30%) along curved tissues, and limited sensitivity to detect targets consistently. Herein, a Gen-2 hand-held optical imager that overcame the above limitations of the Gen-1 imager has been developed and the instrumentation described. The Gen-2 hand-held imager is less bulky, portable, and has improved surface contact ( ∼ 86%) on curved tissues. Additionally, the forked probe head design is capable of simultaneous bilateral reflectance imaging of both breast tissues, and also transillumination imaging of a single breast tissue. Experimental studies were performed on tissue phantoms to demonstrate the improved sensitivity in detecting targets using the Gen-2 imager. The improved instrumentation of the Gen-2 imager allowed detection of targets independent of their location with respect to the illumination points, unlike in Gen-1 imager. The developed imager has potential for future clinical breast imaging with enhanced sensitivity, via both reflectance and transillumination imaging.
Hand-held optical imaging devices are currently developed by several research groups as a noninvasive and non-ionizing
method towards clinical imaging of breast cancer. The devices developed to date are typically utilized towards
spectroscopic imaging via reflectance-based measurements. Additionally, a couple of devices have been used to perform
3D tomography with the addition of a second modality (e.g. ultrasound). A hand-held optical device that is unique in its
ability to perform rapid 2D imaging and 3D tomography (without the use of a second modality) has been developed in
our Optical Imaging laboratory. Herein, diffuse optical imaging studies are performed in breast cancer subjects. For
these studies, the subject lay in a recliner chair and both breast tissues were imaged with the hand-held optical device
which uses 785 nm laser source and an intensified CCD camera-based detector. Preliminary results demonstrate the
ability to image invasive ductal carcinoma and lymphatic spread, as compared to the patient's medical records (e.g. xray,
ultrasound, MRI). Multiple imaging studies with a subject undergoing chemotherapy demonstrated the potential to
monitor response to treatment. Currently, studies are carried out to tomographically determine the 3D location of the
tumor(s) in breast cancer subjects using the hand-held optical device.
Autism is a socio-communication brain development disorder. It is marked by degeneration in the ability to respond to
joint attention skill task, from as early as 12 to 18 months of age. This trait is used to distinguish autistic from nonautistic.
In this study Near infrared spectroscopy (NIRS) is being applied for the first time to study the difference in
activation and connectivity in the frontal cortex of typically developing (TD) and autistic children between 4-8 years of
age in response to joint attention task. The optical measurements are acquired in real time from frontal cortex using
Imagent (ISS Inc.) - a frequency domain based NIRS system in response to video clips which engenders a feeling of joint
attention experience in the subjects. A block design consisting of 5 blocks of following sequence 30 sec joint attention
clip (J), 30 sec non-joint attention clip (NJ) and 30 sec rest condition is used. Preliminary results from TD child shows
difference in brain activation (in terms of oxy-hemoglobin, HbO) during joint attention interaction compared to the nonjoint
interaction and rest. Similar activation study did not reveal significant differences in HbO across the stimuli in,
unlike in an autistic child. Extensive studies are carried out to validate the initial observations from both brain activation
as well as connectivity analysis. The result has significant implication for research in neural pathways associated with
autism that can be mapped using NIRS.
Near Infrared Spectroscopy (NIRS) offers an invaluable tool to monitor the functionality of the brain. NIRS with its
high temporal resolution and good spatial resolution has been applied towards various area of brain research in order
to map the cortical regions of the brain. The present study is aimed at using NIRS to understand the functionality of
the temporal cortex in response to language-related tasks. A 32-channel NIRS system (Imagent ISS Inc.) is used to
perform experimental studies on 15 normal adults. A block-design based Word Expression and Word Reception
tasks were independently presented to the participants during the imaging study. Unlike past research where only
the brain activation was determined for language tasks, in the current study the activation, connectivity, and
lateralization in the temporal cortex are correlated. In the future, the work is focused to target the pediatric epileptic
populations, where understanding the temporal brain functionality in response to language is essential in pre-surgical
clinical environment.
Proc. SPIE. 7896, Optical Tomography and Spectroscopy of Tissue IX
KEYWORDS: Breast, Human subjects, 3D acquisition, Tissues, Imaging systems, Tomography, Optical tomography, In vivo imaging, Tissue optics, 3D image processing
Hand-held optical imagers are currently developed toward clinical imaging of breast tissue. However, the hand-held
optical devices developed to are not able to coregister the image to the tissue geometry for 3D tomography. We have
developed a hand-held optical imager which has demonstrated automated coregistered imaging and 3D tomography in
phantoms, and validated coregistered imaging in normal human subjects. Herein, automated coregistered imaging is
performed in a normal human subject with a 0.45 cm3 spherical target filled with 1 μM indocyanine green (fluorescent
contrast agent) placed superficially underneath the flap of the breast tissue. The coregistered image data is used in an
approximate extended Kalman filter (AEKF) based reconstruction algorithm to recover the 3D location of the target
within the breast tissue geometry. The results demonstrate the feasibility of performing 3D tomographic imaging and
recovering a fluorescent target in breast tissue of a human subject for the first time using a hand-held based optical
imager. The significance of this work is toward clinical imaging of breast tissue for cancer diagnostics and therapy
monitoring.
Autism is a socio-communication brain development disorder. It is marked by degeneration in the ability to respond to
joint attention skill task, from as early as 12 to 18 months of age. This trait is used to distinguish autistic from nonautistic
populations. In this study, diffuse optical imaging is being used to study brain connectivity for the first time in
response to joint attention experience in normal adults. The prefrontal region of the brain was non-invasively imaged
using a frequency-domain based optical imager. The imaging studies were performed on 11 normal right-handed adults
and optical measurements were acquired in response to joint-attention based video clips. While the intensity-based
optical data provides information about the hemodynamic response of the underlying neural process, the time-dependent
phase-based optical data has the potential to explicate the directional information on the activation of the brain. Thus
brain connectivity studies are performed by computing covariance/correlations between spatial units using this
frequency-domain based optical measurements. The preliminary results indicate that the extent of synchrony and
directional variation in the pattern of activation varies in the left and right frontal cortex. The results have significant
implication for research in neural pathways associated with autism that can be mapped using diffuse optical imaging
tools in the future.
Proc. SPIE. 7555, Advanced Biomedical and Clinical Diagnostic Systems VIII
KEYWORDS: Target detection, Breast, Tissues, Imaging systems, Luminescence, Tomography, In vivo imaging, Natural surfaces, In vitro testing, 3D image processing
A hand-held optical imaging device has been developed in our laboratory towards fast 2D imaging and 3D tomography
for breast cancer diagnosis. The device has the unique abilities: (1) to contour to different tissue curvatures using a
flexible probe face; (2) perform fast 2D imaging by employing simultaneous over sequential source illumination; and
(3) self coregistration towards (future) 3D tomography. The objective of the current work is to demonstrate fast
coregistered 2D imaging on breast tissue of healthy female subjects. Fluorescence imaging experiments are performed
in vitro and in vivo to demonstrate coregistered imaging as well as the ability to detect deep targets from multiple surface
scans. A 0.45 cc spherical target filled with 1 μM indocyanine green is embedded at various depths of a cubical phantom
filled with chicken breast (in vitro models). For in vivo studies, the fluorescent target is placed under the flap of the
breast tissue to represent a tumor for fluorescence imaging. Multiple scans (fast continuous-wave images of
fluorescence intensity) are collected and coregistered at different locations on the breast tissue. This study demonstrates
the potential of the hand-held optical device towards future in vivo surface imaging and tomographic imaging for 3D
tumor localization.
Several hand-held based optical imaging devices have been developed towards breast imaging, which are portable,
patient-comfortable, and use non-ionizing radiation. The devices developed to date are limited in that they have flat
probe faces and are incapable of real-time coregistration (as needed for 3-D tomographic imaging). A hand-held based
optical imager has been developed in our lab, which has unique features of (i) simultaneous over sequential source
illumination, which enables rapid data acquisition, (ii) a flexible probe face, which enables it to contour to any tissue
curvature, and (iii) self coregistration facilities towards 3-D tomographic imaging. Real-time coregistration is
demonstrated using the imager via fluorescence-enhanced studies in the continuous-wave mode, performed on slab
phantoms (filled with 1% Liposyn solution) and in vitro samples (chicken breast). Additionally, preliminary studies
were conducted using curved phantoms. In all cases, a 0.45-cc target filled with 1 μM Indocyanine green was used to
represent a tumor. Real-time 2-D surface images of the phantom were obtained via multiple scans at different target
depths. Preliminary surface imaging studies demonstrated that the summation of multiple scans distinctly differentiated
the target from artifacts (up to 3 cm deep), which was not possible from individual scans.
In the current research, diffuse optical imaging (DOI) is used for the first time towards studies related to sociocommunication
impairments, which is a characteristic feature of autism. DOI studies were performed on normal adult
volunteers to determine the differences in the brain activation (cognitive regions) in terms of the changes in the cerebral
blood oxygenation levels in response to joint and non-joint attention based stimulus (i.e. socio-communicative
paradigms shown as video clips). Functional connectivity models are employed to assess the extent of synchronization
between the left and right pre-frontal regions of the brain in response to the above stimuli.
Hand-held based optical imagers have become a new research interest for its maximum patient comfort, less bulky
instrument and potential for clinical translation towards breast cancer diagnostics. However, its ability for optical
tomography is either limited by depth recovery since only reflectance measurements were obtained using a hand-held
design for imaging. In this study, we introduced a self-guided
multi-projection technique, which can take advantage of
potential portability of hand-held probe based system, towards improvement of target depth recovery during
fluorescence optical tomography studies.
Near-infrared (NIR) optical imaging is an emerging noninvasive modality for breast cancer diagnosis. The currently
available optical imaging systems towards tomography studies are limited either by instrument portability, patient
comfort, or flexibility to image any given tissue volume. Hence, a novel hand-held probe based gain modulated
intensified CCD camera imaging system is developed such that it can possibly overcome some of the above limitations.
The unique features of this hand-held probe based optical imaging system are: (i) to perform simultaneous multiple point
illumination and detection, thus decreasing the total imaging time and improving overall signal strength; (ii) to adapt to
the tissue contours, thus decreasing the light leakage at contact surface; and (iii) to obtain trans-illumination
measurements apart from reflectance measurements, thus improving the depth information. Phantom studies are
performed to demonstrate the feasibility of performing fluorescence optical imaging under different target depths using
cubical phantoms (10×6.5×10 cc). The effect of simultaneous multiple point illumination over sequential single point
illumination is demonstrated from experimental phantom studies.
Near-infrared optical imaging is an emerging noninvasive technology toward breast cancer diagnosis. The optical imaging systems available to date are limited either by flexibility to image any given breast volume, patient comfort, or instrument portability. Here, a hand-held optical probe is designed and developed, 1. employing a unique measurement scheme of simultaneous multiple point illumination and collection for rapid data acquisition and minimal patient discomfort, and 2. employing a curved probe head such that it allows flexible imaging of tissue curvatures. Simulation studies are carried out on homogeneous slab phantoms (5×10×8 cc) to determine an appropriate source-detector configuration for the probe head. These design features are implemented in the development of the probe, which consisted of six simultaneous illuminating and 165 simultaneous collecting fibers, spaced 0.5 cm apart on a 5×10 sq-cm probe head. Simulation studies on 3-D slab and curved phantoms demonstrate an increase in the total area of predicted fluorescence amplitude and overall signal strength on using simultaneous multiple point sources over a single point source. The probe is designed and developed such that on coupling with a detection system in the future, the hand-held probe based imager can be clinically assessed toward cancer diagnostic imaging.
Near-infrared (NIR) optical imaging is an emerging noninvasive modality for breast cancer diagnosis. However, the
currently available optical imaging systems towards tomography studies are limited either by instrument portability,
patient comfort, or flexibility to image any given tissue volume. Herein, a hand-held based optical imaging system is
developed such that it can possibly overcome some of the above limitations. The unique features of the hand-held
optical probe are: (i) to perform simultaneous multiple point illumination and detection, thus decreasing the total imaging
time and improving the overall signal strength; (ii) to adapt to the contour of tissue surface, thus decreasing the leakage
of excitation and emission signal at contact surface; and (iii) to obtain trans-illumination measurements apart from
reflectance measurements, thus improving the depth information. The increased detected signal strength as well as total
interrogated tissue volume is demonstrated by simulation studies (i.e. forward model) over a 5×10×10 cc slab phantom.
The appropriate number and layout of the source and detection points on the probe head is determined and the hand-held
optical probe is developed. A frequency-domain ICCD (intensified charge coupled device) detection system, which
allows simultaneous multiple points detection, is developed and coupled to the hand-held probe in order to perform
fluorescence-enhanced optical imaging of tissue phantoms. In the future, imaging of homogenous liquid phantoms will
be used for the assessment of this hand-held system, followed by extensive imaging studies on different phantoms types
under various experimental conditions.
We demonstrate fluorescence-enhanced optical imaging of single and multiple fluorescent targets within a large (~1081 cm3) phantom using frequency-domain photon migration measurements of fluorescence collected at individual points in response to illumination of excitation light at individual points on the boundary. The tissue phantom was filled with a 1% lipid solution with and without 0.01 µM Indocyanine Green (ICG) and targets consisted of vials filled with the 1% lipid containing 1–2.5 µM ICG. Measurements were acquired using a modulated intensified CCD imaging system under different experimental conditions. For 3-D image reconstruction, the gradient-based penalty modified barrier function (PMBF) method with simple bounds constrained truncated Newton with trust region method (CONTN) was used. Targets of 0.5, 0.6, and 1.0 cm3 at depths of 1.4–2.8 cm from the phantom surface were tomographically reconstructed. This work demonstrates the practicality of fluorescence-enhanced tomography in clinically relevant volumes.
Fluorescence-enhance optical tomography is performed using (i) point illumination and point collection and (ii) area illumination and area collection geometrics in 3D. In both measurement techniques, an image-intensified charge-coupled (ICCD) imaging system is used in the frequency-domain to image near-infrared contrast agents. The experimental measurements are compared to diffusion model predictions in least squares form in the inverse problem. For image recovery for both area and point illumination geometries, an efficient gradient-based optimization technique based on the Penalty/modified barrier function (PMBF) method and the constrained truncated Newton with trust region (CONTN) method is developed. Targets in 3D were reconstructed from experimental data under two conditions of (i) perfect uptake (1:0, target to background ratio) and (ii) imperfect uptake (100:1, target to background ratio). Parameters of absorption cross section due to fluorophore and lifetimes are reconstructed. The present work demonstrates that 3D fluorescence enhanced optical tomography reconstructions can be successfully performed from both point/area illumination and collection experimental measurements of the time-dependent light propagation on clinically relevant tissue phantoms using a gain-modulated ICCD camera.
Molecular targeting with exogenous near-infrared excitable fluorescent agents using time-dependent imaging techniques may enable diagnostic imaging of breast cancer and prognostic imaging of sentinel lymph nodes within the breast. However, prior to the administration of unproven contrast agents, phantom studies on clinically relevant volumes are essential to assess the benefits of fluorescence-enhanced optical imaging in humans. Diagnostic 3-D fluorescence-enhanced optical tomography is demonstrated using 0.5 to 1 cm3 single and multiple targets differentiated from their surroundings by indocyanine green (micromolar) in a breast-shaped phantom (10-cm diameter). Fluorescence measurements of referenced ac intensity and phase shift were acquired in response to point illumination measurement geometry using a homodyned intensified charge-coupled device system modulated at 100 MHz. Bayesian reconstructions show artifact-free 3-D images (3857 unknowns) from 3-D boundary surface measurements (126 to 439). In a reflectance geometry appropriate for prognostic imaging of lymph node involvement, fluorescence measurements were likewise acquired from the surface of a semi-infinite phantom (8×8×8 cm3) in response to area illumination (12 cm2) by excitation light. Tomographic 3-D reconstructions (24,123 unknowns) were recovered from 2-D boundary surface measurements (3194) using the modified truncated Newton's method. These studies represent the first 3-D tomographic images from physiologically relevant geometries for breast imaging.
Proc. SPIE. 4949, Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems XIII
KEYWORDS: Optical fibers, Refractive index, 3D image reconstruction, Data modeling, Imaging systems, Cameras, Interfaces, 3D modeling, Tomography, Data acquisition
A frequency-domain photon migration (FDPM) imager employing an image-intensified CCD camera for fast data acquisition on a large tissue-mimicking phantom (1087 ml) is described. Fluorescence-enhanced imaging is performed employing frequency-domain techniques at 100 MHz in order to obtain the boundary measurements of phase and amplitude and to recover the interior optical maps using the first principles of light propagation. The effect of refractive-index parameter in the boundary condition of the light propagation model is not significant due to the large phantom volume and its curvilinear nature. Initial experiments were performed under perfect (1:0 contrast) and imperfect (100:1 contrast) uptake cases using indocyanine green as the contrast agent. Preliminary 3D image reconstructions using the approximate extended Kalman filter (AEKF) algorithm are presented.
The approximate extended Kalman filter (AEKF) has been suggested as an appropriate inverse method for reconstructing fluorescent properties in large tissue samples from frequency domain data containing measurement error. The AEKF is an “optimal” estimator, in that it seeks to minimize the predicted error variances of the estimated optical properties in relation to measurement and system errors. However, due to non-linearities in the recursive estimation process, the updates are actually suboptimal. Furthermore, the computational overhead is large for the full AEKF algorithm when applied to large datasets. In this contribution we developed three hybrid forms of the AEKF algorithm that may improve the performance in frequency domain fluorescence tomography. Numerical results of image reconstruction from actual frequency domain emission data show that one hybrid form of the AEKF outperforms the traditional full AEKF in both image quality and computational efficiency for the two cases tested.
We present results of ongoing research in 3-D fluorescence tomography on large clinically-relevant tissue-mimicking domains. Finite element predictions of excitation and emission phase shift and amplitude attenuation are compared to experimental data from both column-shaped and breast-shaped tissue mimicking phantoms containing embedded fluorophore; system noise and measurement noise are characterized and utilized in image reconstruction using the Bayesian APPRIZE algorithm.
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