G. Reed Holyoak

Trans-rectal ultrasound-coupled near-infrared optical tomography of the prostate Part II: Experimental demonstration

We demonstrate trans-rectal optical tomography of the prostate using an endo-rectal near-infrared (NIR) applicator integrated with a transrectal ultrasound (TRUS) probe. The endo-rectal NIR applicator incorporated a design presented in our previously reported work. A continuous-wave NIR optical tomography system is combined with a commercial US scanner to form the dual-modality imager. Sagittal transrectal imaging is performed concurrently by endo-rectal NIR and TRUS. The TRUS ensures accurate positioning of the NIR applicator as well as guides NIR image reconstruction using the spatial prior of the target. The use of a condom, which is standard for TRUS, is found to have minimal effect on trans-rectal NIR imaging. Tests on avian tissues validates that NIR imaging can recover the absorption contrast of a target, and its accuracy is improved when the TRUS spatial prior is incorporated. Trans-rectal NIR/US imaging of a healthy canine prostate in situ is reported.

In vivo trans-rectal ultrasound-coupled optical tomography of a transmissible venereal tumor model in the canine pelvic canal

In vivo trans-rectal near-infrared (NIR) optical tomography was performed concurrently with, albeit reconstructed without spatial a prior of, trans-rectal ultrasound (US) on transmissible venereal tumor (TVT) developed as a model in the canine pelvic canal. Studies were taken longitudinally at prior to, 14 days after, and 35 days after the TVT injection. As the tumor grew, the nodules became increasingly hyperabsorptive and moderately hyperscattering on NIR. The regions of strong NIR contrast, especially on absorption images, correlated well with those of US hypoechoic masses indicative of tumors. Combining the information of trans-rectal NIR and US detected the tumor more accurately than did the US alone at 14 days postinjection.

In vivo trans-rectal ultrasound-coupled near-infrared optical tomography of intact normal canine prostate

This is the first tomography-presentation of the optical properties of a normal canine prostate, in vivo, in its native intact environment in the pelvic canal. The imaging was performed by trans-rectal near-infrared (NIR) optical tomography in steady-state measurement at 840 nm on three sagittal planes across the right lobe, middle-line, and left lobe, respectively, of the prostate gland. The NIR imaging planes were position-correlated with concurrently applied trans-rectal ultrasound, albeit there was no spatial prior employed in the NIR tomography reconstruction. The reconstructed peak absorption coefficients of the prostate on the three planes were 0.014, 0.012, and 0.014 mm-1. The peak reduced scattering coefficients were 5.28, 5.56, and 6.53 mm-1. The peak effective attenuation coefficients were 0.45, 0.43, and 0.50 mm-1. The absorption and effective attenuation coefficients were within the ranges predictable at 840 nm by literature values which clustered sparsely from 355 nm to 1064 nm, none of which were performed on a canine prostate with similar conditions. The effective attenuation coefficients of the gland were shown to be generally higher in the internal aspects than in the peripheral aspects, which is consistent with the previous findings that the urethral regions were statistically more attenuating than the capsular regions.

Near-infrared optical tomography: endoscopic imaging approach

Near-infrared optical tomography is an interesting technique of imaging with high blood-based contrast. Unfortunately non-invasive NIR tomographic imaging has been restricted to specific organs like breast that can be transilluminated externally. In this paper, we demonstrate that near-infrared (NIR) optical tomography can be employed at the endoscope-scale, and implemented at a rapid sampling speed that allows translation to in vivo use. A spread-spectral-encoding technique based on a broadband light source is combined with light delivery by linear-to-circular fiber bundle, to provide endoscopic probing of multiple source/detector fibers for tomographic imaging as well as parallel sampling of all source-detector pairs for rapid data acquisition. Endoscopic NIR tomography is demonstrated by use of a 12mm diameter probe housing 8 sources and 8 detectors at 8 Hz frame rate. Transrectal NIR optical tomography by use of tissue specimen is also presented. This novel approach provides the key feasibility studies to allow this blood-based contrast imaging technology to be tried in cancer detection of internal organs via endoscopic interrogation.

In vivo trans-rectal ultrasound coupled trans-rectal near-infrared optical tomography of canine prostate bearing transmissible venereal tumor

In vivo trans-rectal near-infrared (NIR) optical tomography is conducted on a tumor-bearing canine prostate with the assistance of trans-rectal ultrasound (TRUS). The canine prostate tumor model is made possible by a unique round cell neoplasm of dogs, transmissible venereal tumor (TVT) that can be transferred from dog to dog regardless of histocompatibility. A characterized TVT cell line was homogenized and passed twice in subcutaneous tissue of NOD/SCID mice. Following the second passage, the tumor was recovered, homogenized and then inoculated by ultrasound guidance into the prostate gland of a healthy dog. The dog was then imaged with a combined trans-rectal NIR and TRUS imager using an integrated trans-rectal NIR/US applicator. The image was taken by NIR and US modalities concurrently, both in sagittal view. The trans-rectal NIR imager is a continuous-wave system that illuminates 7 source channels sequentially by a fiber switch to deliver sufficient light power to the relatively more absorbing prostate tissue and samples 7 detection channels simultaneously by a gated intensified high-resolution CCD camera. This work tests the feasibility of detecting prostate tumor by trans-rectal NIR optical tomography and the benefit of augmenting TRUS with trans-rectal NIR imaging.

In vivo assessment of diet-induced rat hepatic steatosis development by percutaneous single-fiber spectroscopy detects scattering spectral changes due to fatty infiltration

Abstract. This study explores percutaneous single-fiber spectroscopy (SfS) of rat livers undergoing fatty infiltration. Eight test rats were fed a methionine-choline-deficient (MCD) diet, and four control rats were fed a normal diet. Two test rats and one control rat were euthanized on days 12, 28, 49, and 77 following initiation of the diet, after percutaneous SfS of the liver under transabdominal ultrasound guidance. Histology of each set of the two euthanized test rats showed mild and mild hepatic lipid accumulations on day 12, moderate and severe on day 28, severe and mild on day 49, and moderate and mild on day 77. Livers with moderate or higher lipid accumulation generally presented higher spectral reflectance intensity when compared to lean livers. Livers of the eight test rats on day 12, two of which had mild lipid accumulation, revealed an average scattering power of 0.37±0.14 in comparison to 0.07±0.14 for the four control rats (p<0.01). When livers of the test rats with various levels of fatty infiltration were combined, the average scattering power was 0.36±0.15 in comparison to 0.14±0.24 of the control rats (0.05<p<0.1). Increasing lipid accumulation in concentration and size seemed to cause an increase of the scattering power prior to increasing total spectral reflectance.

Different optical spectral characteristics in a necrotic transmissible venereal tumor and a cystic lesion in the same canine prostate observed by triple-band trans-rectal optical tomography under trans-rectal ultrasound guidance

Different optical spectral characteristics were observed in a necrotic transmissible venereal tumor (TVT) and a cystic lesion in the same canine prostate by triple-wavelength trans-rectal optical tomography under trans-rectal ultrasound (TRUS) guidance. The NIR imager acquiring at 705nm, 785nm and 808nm was used to quantify both the total hemoglobin concentration (HbT) and oxygen saturation (StO2) in the prostate. The TVT tumor in the canine prostate as a model of prostate cancer was induced in a 7-year old, 27 kg dog. A 2 mL suspension of 2.5x106 cells/mL of homogenized TVT cells recovered from an in vivo subcutaneously propagated TVT tumor in an NOD/SCID mouse were injected in the cranial aspect of the right lobe of the canine prostate. The left lobe of the prostate had a cystic lesion present before TVT inoculation. After the TVT homogenate injection, the prostate was monitored weekly over a 9-week period, using trans-rectal NIR and TRUS in grey-scale and Doppler. A TVT mass within the right lobe developed a necrotic center during the later stages of this study, as the mass presented with substantially increased [HbT] in the periphery, with an area of reduced StO2 less than the area of the mass itself shown on ultrasonography. Conversely, the cystic lesion presented with slightly increased [HbT] in the periphery of the lesion shown on ultrasound with oxygen-reduction inside and in the periphery of the lesion. There was no detectable change of blood flow on Doppler US in the periphery of the cystic lesion. The slightly increased [HbT] in the periphery of the cystic lesion was correlated with intra-lesional hemorrhage upon histopathologic examination.

A laparoscopic applicator probe for real-time en-face mapping of near-surface optical sources of heterogeneity over a 1cm instrument-tip-size field-of-view

Surgeons operating laparoscopically often have to rely upon subjective visual cues for complete oncological control and avoiding tumor violation or iatrogenic injury to critical tissues. A laparoscopic imaging tool to allow assessment of tumor margin or identification of anatomical structures buried under the layer of tissue being dissected is desirable to probe tissue contrast at a few millimeters depth, visualize over the lateral view for resection guidance, have a non-microscopic field-of-view (FOV) adequate for rapid survey of the resection site, and form the image in real-time. Probing light diffusely propagated through tissue provides sub-surface sensitivity, but the image formation generally involves intense computation that may be costly to intraoperative time-frame. Projecting these modalities laparoscopically to sample subsurface tissue heterogeneity over a non-microscopic FOV for rapid site-survey has been challenging. We demonstrate a laparoscopic applicator probe and a method thereof for real-time en-face mapping of near-surface heterogeneity for potential use towards intraoperative margin assessment. The probe fits a 12mm port and houses at 128 copper-coated 750μm fibers that form radially alternating illumination (70 fibers) and detection (58 fibers) channels. By simultaneously illuminating the 70 source channels of the laparoscopic probe that is in contact with a scattering medium and concurrently measuring the light diffusely propagated to the 58 detector channels, the presence of near-surface optical heterogeneities can be resolved in an en-face 9.5mm field-of-view in real-time. Visualization of subsurface margin of strong attenuation contrast at a depth up to 3mm is demonstrated at a frame rate of 1.25Hz.

In vivo percutaneous single fiber spectroscopy of fatty changes of livers in a rat model of diet-induced hepatic steatosis

Percutaneous single-fiber spectroscopy was applied in vivo to livers of rats fed a control diet (8 rats) and a methionine-choline-deficient diet (16 rats). Lipid accumulation was associated with changes in spectroscopy-extracted scattering parameters.

Optical biopsy of the prostate: can we TRUST (trans-rectal ultrasound-coupled spectral tomography)?

Needle-based core-biopsy to locate prostate cancer relies heavily upon trans-rectal ultrasound (TRUS) imaging guidance. Ultrasonographic findings of classic hypoechoic peripheral zone lesions have a low specificity of ~28%, a low positive predictive value of ~29%, and an overall accuracy of ~43%, in prostate cancer diagnosis. The prevalence of isoechoic or nearly invisible prostate cancers on ultrasonography ranges from 25 to 42%. As a result, TRUS is useful and convenient to direct the needle trajectory following a systematic biopsy sampling template rather than to target only the potentially malignant lesion for focal-biopsy. To address this deficiency in the first-line of prostate cancer imaging, a trans-rectal ultrasound-coupled spectral tomography (TRUST) approach is being developed to non-invasively resolve the likely optical signatures of prostate malignancy. The approach has evolved from using one NIR wavelength to two NIR bands, and recently to three bands of NIR spectrum information. The concept has been evaluated on one normal canine prostate and three dogs with implanted prostate tumor developed as a model. The initial results implementing TRUST on the canine prostate tumor model includes: (1) quantifying substantially increased total hemoglobin concentration over the time-course of imaging in a rapidly growing prostate tumor; (2) confirming hypoxia in a prostatic cystic lesion; and (3) imaging hypoxic changes of a necrotic prostate tumor. Despite these interesting results, intensive technologic development is necessary for translating the approach to benefiting clinical practice, wherein the ultimate utility is not possibly to eliminate needle-biopsy but to perform focal-biopsy that is only necessary to confirm the cancer, as well as to monitor and predict treatment responses.