Toward transduodenal diffuse optical tomography of proximal pancreas

We demonstrate the feasibility of diffuse optical tomography (DOT) of the proximal pancreas by using optical applicator channels deployed longitudinally along the exterior surface of a duodenoscope. As the duodenum that nearly encircles the proximal pancreas forms a natural "C-loop" that is approximately three-quarters of a circle of 5-6 cm in diameter, a multichannel optical applicator attached to a duodenoscope has the potential to perform transduodenal DOT sampling of the bulk proximal pancreas wherein most cancers and many cystic lesions occur. The feasibility of transduodenal DOT is demonstrated on normal porcine pancreas tissues containing an introduced gelatinous inclusion of approximately 3 cm in diameter, by using nine source channels and six detector channels attached to a duodenoscope. Concurrent ultrasonography of the gelatinous inclusion in the porcine pancreas parenchyma provided a coarse, albeit indispensable, anatomic prior to transduodenal DOT in reconstructing a contrast of optical properties in the pancreas.Electrical and Computer EngineeringVeterinary Clinical Science

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

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.Electrical and Computer EngineeringVeterinary Clinical Science

Transrectal ultrasound-integrated spectral optical tomography of hypoxic progression of a regressing tumor in a canine prostate

The objective of this study was to evaluate if transrectal optical tomography implemented at three wavelength bands for spectral detection could monitor changes of the hemoglobin oxygen saturation (SₜO₂) in addition to those of the total hemoglobin concentration ([HbT]) in lesions of a canine prostate, including an induced tumor modeling canine prostate cancer. Near-infrared (NIR) optical tomography was integrated with ultrasound (US) for transrectal imaging. Multi-spectral detection at 705 nm, 785 nm and 808 nm rendered measurements of [HbT] and SₜO₂. Canine transmissible venereal tumor (TVT) cells were injected into the right lobe of a dog's prostate gland, which had a pre-existing cyst in the left lobe. Longitudinal assessments of the prostate were performed weekly over a 63-day duration by NIR imaging concurrent with grey-scale and Doppler US. Ultrasonography revealed a bi-lobular tumor-mass regressing from day-49 to day-63. At day-49 this tumor-mass developed a hypoxic core that became larger and more intense by day-56 and expanded further by day-63. The tumor-mass presented a strong hyper-[HbT] feature on day-56 that was inconsistent with US-visualized blood flow. Histology confirmed two necrotic TVT foci within this tumor-mass. The cyst appeared to have a large anoxic-like interior that was greater in size than its ultrasonographically delineated lesion, and a weak lesional elevation of [HbT]. On day-56, the cyst presented a strong hyper-[HbT] feature consistent with US-resolved blood flow. Histology revealed acute and chronic hemorrhage in the periphery of the cyst. The NIR imaging features of two other TVT nodules and a metastatic lymph node were evaluated retrospectively. Transrectal US-integrated spectral optical tomography seems to enable longitudinal monitoring of intra-lesional oxygenation dynamics in addition to the hemoglobin content of lesions in the canine prostate.Electrical & Computer EngineeringVeterinary Clinical Science

In vivo percutaneous reflectance spectroscopy of fatty liver development in rats suggests that the elevation of the scattering power is an early indicator of hepatic steatosis

This study assessed whether there was a scattering spectral marker quantifiable by reflectance measurements that could indicate early development of hepatic steatosis in rats for potential applications to pre-procurement organ evaluation. Sixteen rats were fed a methionine-choline-deficient (MCD) diet and eight rats were fed a normal diet. Direct assessment of the liver parenchyma of rats in vivo was performed by percutaneous reflectance spectroscopy using a single fiber probe at the beginning of diet-intake and arbitrary post-diet-intake times up to 11 weeks to render longitudinal comparison. Histological sampling of the liver over the duration of diet administration was performed on two MCD-diet treated rats and one control rat euthanized after reflectance spectroscopy measurement. The images of hematoxylin/eosin-stained liver specimens were analyzed morphometrically to evaluate the lipid size changes associated with the level of steatosis. The MCD-diet-treated group (n=16) had mild steatosis in seven rats, moderate in three rats, severe in six rats, and no other significant pathology. No control rats (n=8) developed hepatic steatosis. Among the parameters retrieved from per-SfS, only the scattering power (can be either positive or negative) appeared to be statistically different between MCD-treated and control livers. The scattering power for the 16 MCD-diet-treated livers at the time of euthanasia and presenting various levels of steatosis was 0.33±0.21, in comparison to 0.036±0.25 of the eight control livers (p=0.0189). When evaluated at days 12 and 13 combined, the scattering power of the 16 MCD-diet-treated livers was 0.32±0.17, in comparison to 0.10±0.11 of the eight control livers (p=0.0017). All of four MCD-treated livers harvested at days 12 and 13 presented mild steatosis with sub-micron size lipid droplets, even though none of the MCD-treated livers were sonographically remarkable for fatty changes. The elevation of the scattering power may be a valuable marker indicating early hepatic steatosis before the steatosis is sonographically detectable.Electrical and Computer EngineeringVeterinary Clinical Science

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.Veterinary Clinical SciencesElectrical and Computer Engineerin

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.Electrical and Computer EngineeringVeterinary Clinical Science

Structural changes in the progression of atrial fibrillation: Potential role of glycogen and fibrosis as perpetuating factors

Background: Previous studies of the goat heart subjected to prolonged atrial pacing induced sustained atrial fibrillation (AF). Structural changes included marked accumulation of glycogen in atrial myocytes. Aims: In the present study, we hypothesized that glycogen deposition in canine atrial myocytes promotes paroxysmal forms of AF and is involved in fibrosis development in the later stages of AF. Material & methods: In dogs under pentobarbital anesthesia, tissues were obtained from the right and left atrial appendages (LAA/RAA). Periodic acid Schiff (PAS) and Masson's trichrome staining of the LAA/RAA from normal dogs, and those subjected to atrial pacing induced AF for 48 h or 8 weeks determined glycogen and collagen concentrations, respectively, using morphometric analysis. Results: At baseline, there was a significant greater concentration of glycogen in the LAA than the RAA (P </= 0.05). Compared to the RAA, the LAA glycogen, was dense and locked against the intercalated discs. After pacing induced AF for 48 hours and 8 weeks there was a marked increase in glycogen deposition, significantly greater than in the baseline state (P </= 0.05). There was a similar and progressive increase in collagen concentrations in each group (P </= 0.05). Conclusions: The differential in glycogen concentration, in conjunction with other factors, neural and electrophysiological, provide a basis for the greater propensity of the left atrium for paroxysmal AF, at baseline and 48 hours of pacing induced AF. The marked increase in collagen at 8 weeks of pacing provides a substrate for sustained AF. Evidence is presented linking glycogen accumulation and fibrosis as factors in the persistent forms of AF.Peer reviewedVeterinary Pathobiolog

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.Electrical and Computer EngineeringVeterinary Clinical Science

Immune responses to influenza D virus in calves previously infected with bovine viral diarrhea virus 2

Bovine viral diarrhea virus (BVDV) induces immunosuppression and thymus depletion in calves. This study explores the impact of prior BVDV-2 exposure on the subsequent immune response to influenza D virus (IDV). Twenty 3-week-old calves were divided into four groups. Calves in G1 and G3 were mock-treated on day 0, while calves in G2 and G4 received BVDV. Calves in G1 (mock) and G2 (BVDV) were necropsied on day 13 post-infection. IDV was inoculated on day 21 in G3 calves (mock + IDV) and G4 (BVDV + IDV) and necropsy was conducted on day 42. Pre-exposed BVDV calves exhibited prolonged and increased IDV shedding in nasal secretions. An approximate 50% reduction in the thymus was observed in acutely infected BVDV calves (G2) compared to controls (G1). On day 42, thymus depletion was observed in two calves in G4, while three had normal weight. BVDV-2-exposed calves had impaired CD8 T cell proliferation after IDV recall stimulation, and the α/β T cell impairment was particularly evident in those with persistent thymic atrophy. Conversely, no difference in antibody levels against IDV was noted. BVDV-induced thymus depletion varied from transient to persistent. Persistent thymus atrophy was correlated with weaker T cell proliferation, suggesting correlation between persistent thymus atrophy and impaired T cell immune response to subsequent infections.Veterinary PathobiologyDean of Veterinary Medicin

Development of Human Mast Cells from Hematopoietic Stem Cells within a 3D Collagen Matrix: Effect of Stem Cell Media on Mast Cell Generation

Mast cells (MCs) arise from hematopoietic stem cells (HSCs) that mature within vascularized tissues. Fibroblasts and endothelial cells (ECs) play a role in the maturation of HSCs in the tissues. Due to difficulties in isolating MCs from tissues, large numbers of committed MC precursors can be generated in 2D culture systems with the use of differentiation factors. Since MCs are tissue-resident cells, the development of a 3D tissue-engineered model with ancillary cells that more closely mimics the 3D in vivo microenvironment has greater relevance for MC studies. The goals of this study were to show that MCs can be derived from HSCs within a 3D matrix and to determine a media to support MCs, fibroblasts, and ECs. The results show that HSCs within a collagen matrix cultured in StemSpan media with serum added at the last week yielded a greater number of c-kit+ cells and a greater amount of histamine granules compared to other media tested. Media supplemented with serum were necessary for EC survival, while fibroblasts survived irrespective of serum with higher cell yields in StemSpan. This work demonstrates the development of functional MCs within a 3D collagen matrix using a stem cell media that supports fibroblast and ECs