Introduction: Biochemical recurrence of prostate cancer after definitive therapy with radical prostatectomy (RP) is
known to occur between 25-30%. We present the first known case of 1.5T MRI guided ablation using laser interstitial
thermal therapy (LITT) for locally recurrent prostate cancer following RP.
Methods: The patient elected to undergo MRI-guided LITT of the biopsy proven cancer recurrence using an FDAapproved
MRI compatible, 980nm, 15-watt laser system with MR thermometry. Under T2-weighted MR(1.5T Siemens)
imaging, guidance and targeting of the lesions with trans-perineal placement of laser applicators. Multiple cycles of laser
energy were used to ablate the tumor. A MRI-compatible urethral cooling catheter was placed to prevent urethral
Results: Intra-procedural temperature mapping allowed continuous monitoring of the ablation zone and permitted
ablation control until tumor coverage was achieved. Additionally, the protective cooling effects of the urethral cooling
catheter could also be seen with the temperature mapping. Post-ablation gadolinium and T2 weighted MR imaging
demonstrated an ablation defect encompassing the recurrent tumor with no residual hyper-enhancing nodules. Three
month follow-up shows no residual or recurrent tumor seen on MR imaging.
Conclusion: This represents the first known, successful, MRI-guided, LITT procedures at 1.5T for locally recurrent
prostate adenocarcinoma following RP.
We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor
where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal
ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID
mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of
near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the
intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the
intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier.
Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average,
3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8±4.1ºC. Identical laser
doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of
48.6±1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of
nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of
treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.
The reliability of optical techniques for non-invasive monitoring of glucose can be
significantly improved by the deployment of a subcutaneous implantable sensor that can closely
track the changes in the local concentration of glucose in skin. We have developed a novel
implantable sensor that can track glucose-induced changes in the optical turbidity of the implant.
In this sensor, optical turbidity decreases significantly with increased glucose concentrations.
We performed comparative measurements by optical coherence tomography (OCT) used to
monitor backscattering or specular reflection originated from specific structures within the sensor
and by collimated light transmission measurement technique to measure the changes in light
attenuation as function of glucose concentration within the sensor as well as when the sensor was
implanted in phantom media or in tissue samples. These measurements showed that glucose-induced
changes in the transmission values derived from OCT monitoring of the sensor turbidity differed up
two times from those obtained by collimated transparency measurement (CTM) technique. These
results were used to determine the values for scattering coefficients of tissue and the sensor and to
estimate the relative loss in sensor sensitivity as a function of implantation depth in tissue. The
results suggest that the implantable sensor can be placed in turbid medium such as skin up to an
optical depth of 12 mean free paths (mfp), one could expect. For a turbid medium such as skin with a
scattering coefficient (µs ) of 10mm-1, this would result in geometrical depth of implantation at 1.2
mm beneath the tissue where sensor sensitivity of 50% or higher is expected. The study
demonstrates that it could be feasible to engineer a novel optical sensor for glucose monitoring that
can be implanted under the skin while providing a high degree of sensitivity and specificity for non-invasive
Prostate cancer is the most common cancer in American men excluding skin cancer, and approximately 230,000 cases of prostate cancer will be diagnosed in the U.S. in 2004. In the non-surgical treatment of localized prostate cancer, fiberoptically delivered interstitial laser thermal therapy may be ideal for treating discrete tumors with minimal invasiveness. Real-time magnetic resonance imaging can be used to compute temperature changes based on the proton resonance frequency (PRF) shift, and two-dimensional maps of temperature rise and chronic thermal damage can be constructed in order to control laser therapy. In this work, we describe an MRI-compatible percutaneous grid template and localization and planning software for precise placement of minimally invasive laser catheters to effect a target ablation zone. We evaluated the accuracy of the catheter placement, and we present our preliminary experience with percutaneous MRI-guided feedback controlled laser ablation in a canine prostate model. Histological analysis is used to assess the effectiveness and accuracy of treatment visualization.
This work was aimed at exploring the feasibility of MR-guided laser interstitial thermal therapy (LITT) as an adjuvant to vertebroplasty, especially for the management of spinal metastatic tumors. Such a technique may provide a number of advantages including an additional tool for tumor reduction, improved hemostasis, and high precision and safety in thermal therapy. We report on the development of tools and procedures to facilitate augmentation of vertebroplasty with LITT, and we describe the results of laser thermal treatments in normal canine vertebrae.
Minimally invasive thermal therapies for the treatment of prostate cancer offer potential to reduce cost, treatment time, and patient trauma. A drawback to such therapies is that it is often difficult or impossible to know the exact volume of which is being destroyed. In this work, we report on the use of magnetic resonance (MR) thermal imaging to provide real-time feedback control over laser interstitial thermal therapy (LITT) in an in vivo canine prostate model.
Fiber optically delivered laser energy may be ideal in treating small intracerebral lesions with minimal invasiveness. We have continued development of a laser-computer system for automated magnetic resonance thermal imaging (MRTI) guidance and control of intracerebral laser interstitial thermal therapy (LITT). The system consists of a workstation which is interfaced to a clinical MR scanner via Ethernet and to a compact high power diode laser via hardware interface. The system analyzes MRTI data to compute temperature changes based on the proton resonance frequency (PRF) shift, and constructs two-dimensional maps of temperature and estimated chronic thermal damage during therapy. Images are obtained approximately every 4.5 seconds allowing near-real-time tracking of LITT progress. A graphical user interface allows specification of temperature constraints on the image which regulate delivery of thermal energy. We have tested the ability of the system to create small focal intracranial lesions of specified dimension in both normal canine brain (n = 6 animals, 15 lesions) and in an intracerebral tumor model grown from inoculum (n = 11 animals, 15 lesions). Histological analysis was used to assess the accuracy of MRTI-derived predictions of lesion size and to assess effectiveness of reaching prescribed tumor boundaries.
Factors that have limited the acceptance of optical spectroscopy methods for non-invasive blood glucose sensing include signal variations due in part to changes in the skin tissue optics between patients, the lack of a repeatable pathlength inherent in using diffusely reflected photon approaches, temperature variations on the skin, and the pressure with which a probe is applied to the skin surface. Unfortunately, most previous approaches to non-invasive glucose sensing have failed to address these important issues. In this work, we developed a novel skin port sensor (SPS) which eliminates the effect of skin optics by using a stable, infection-free, dermal implant to provide a skinless window into the body. Our implant is designed to provide a fixed optical pathlength as well as features to minimize temperature and pressure variations. Preliminary experiments in a pig model demonstrate both a stable biological seal at the transcutaneous interface as well as ingrowth of vascular containing granulation tissue within the sensing chamber. Furthermore, optical spectra acquired from the port demonstrate changes in glucose signatures related to concentration changes induced in the blood. Our novel SPS may provide the necessary platform for successful implementation of an optical approach to in vivo glucose sensing.
Oral squamous cell carcinoma is a disease which progresses through a number of well-defined morphological and biochemical changes. Optical coherence tomography (OCT) is a rapidly-evolving, non-invasive imaging modality which allows detailed probing of subsurface tissue structures with resolution on the order of microns. While this technique offers tremendous potential as a diagnostic tool for detection and characterization of oral cancer, OCT imaging is presently associated with a field of view on the order of millimeters, and acquisition time on the order of seconds. Thus, OCT's utility as a rapid cancer screening technique is presently limited. On the other hand, imaging of tissue autofluorescence provides a very rapid, high-throughput method for cancer screening. However, while autofluorescence measures may be sensitive to cancer, they are often non- specific and lead to a large number of false positives. In the present work, we have developed a fluorescence image guided optical coherence tomographic (FIG-OCT) probe in which tissue autofluorescence images are simultaneously used to guide OCT image acquisition of suspicious regions in real time. We have begun pre-clinical pilot studies with this instrument in a DMBA-induced model of oral cancer in the hamster cheek pouch. Initial results indicate that the FIG- OCT approach shows promise as a rapid and effective tool for screening of oral cancer.
In the destructive treatment of tumors or other lesions, laser therapies such as laser induced thermal therapy (LITT) or interstitial laser phototherapy (ILP) offer tremendous potential to minimize surgical complications, reduce recovery time and hospital stays, and decrease associated health care costs. While laser procedures have gained wide popularity in dermatology and ophthalmology, their potential has yet to be fully realized in treatment of deep tissues where the damage front created by the laser can not be readily visualized. In the present work, we facilitate this visualization by producing an image of spatial temperature distribution via non-invasive magnetic resonance imaging (MRI). Further, we have implemented a control strategy which allows us to utilize this information for the feedback control of laser thermal therapies. We have begun to explore the feasibility of using this system for improving the safety and efficacy oflaser thermal surgery.
The preliminary design of a noninvasive glucose sensor developed in this investigation was based on the polarization rotation of light produced by optically active molecules. The polarimeter developed for this investigation was unique when compared to previous investigations in that it utilized a single Pockels cell to both modulate the signal and provide feedback within the system. The intended application of this polarimeter is to measure glucose concentrations within the aqueous humor of the eye. The purpose of this investigation was to elucidate whether the theory of superposition and multispectral analysis can be applied to the measurement of glucose in the presence of ascorbic acid and albumin, the most significant rotatory confounders found in the aqueous humor. The results of this investigation indicate that superposition of rotation at different wavelengths due to the above optically active molecules was valid for the in vitro experiments conducted. Utilizing two wavelengths of light, the concentration of hyperglycemic levels of glucose were derived in the presence of physiological concentrations of the optically active confounders ascorbic acid and albumin. It was found, except for one outlier, that the model predicted glucose concentrations to within 23%.