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.
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.
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.
A dual-band trans-rectal optical tomography system is constructed based on an endo-rectal near-infrared/ultrasound
applicator that has been developed previously in our laboratory. The endo-rectal NIR/US applicator consists of a
commercial bi-plane ultrasound and a NIR probe attached to the sagittal ultrasound transducer. The NIR probe consists
of 7 illumination & 7 detection channels that are distributed in parallel to and aside the sagittal TRUS transducer. The
emissions from a 780nm and an 830nm light sources are combined and delivered sequentially to the 7 NIR source
channels of the endo-rectal NIR/US probe. The 7 NIR detection channels are coupled to a spectrometer for separation of
the signals at two wavelengths illuminated from single source channel. The dual-band signals from all source channels
are acquired sequentially by a CCD camera synchronized with the source switching. The acquisition of dual-band trans-rectal
optical tomography data is accompanied by position-correlated concurrent trans-rectal ultrasound imaging. The
reconstruction of a target at dual-wavelength illumination is guided by a priori spatial information provided by the
sagittal trans-rectal ultrasound. Liquid phantoms with different hemoglobin concentration and oxygen saturation are used
to test the feasibility of dual-band trans-rectal optical tomography.
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.
The trans-rectal implementation of NIR optical tomography makes it possible to assess functional status like hemoglobin
concentration and oxygen saturation in prostate non-invasively. Trans-rectal NIR tomography may provide tissue-specific
functional contrast that is potentially valuable for differentiation of cancerous lesions from normal tissues. Such
information will help to determine if a prostate biopsy is needed or can be excluded for an otherwise ambiguous lesion.
The relatively low spatial resolution due to the diffuse light detection in trans-rectal NIR tomography, however, limits
the accuracy of localizing a suspicious tissue volume. Trans-rectal ultrasound (TRUS) is the clinical standard for guiding
the positioning of biopsy needle owing to its resolution and convenience; nevertheless, TRUS lacks the pathognomic
specificity to guide biopsy to only the suspicious lesions. The combination of trans-rectal NIR tomography with TRUS
could potentially give better differentiation of cancerous tissue from normal background and to accurately localize the
cancer-suspicious contrast obtained from NIR tomography. This paper will demonstrate the design and initial evaluation
of a trans-rectal NIR tomography probe that can conveniently integrate with a commercial TRUS transducer. The transrectal
NIR tomography obtained from this probe is concurrent with TRUS at matching sagittal imaging plane. This
design provides the flexibility of simple correlation of trans-rectal NIR with TRUS, and using TRUS anatomic
information as spatial prior for NIR image reconstruction.
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