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Biomedical subjects

Erik R Wisner

Publications and source records attributed to Erik R Wisner.

At least 19 recordsLinked to original sources

Results of rhinoscopy alone or in conjunction with sinuscopy in dogs with aspergillosis: 46 cases (2001-2004).

OBJECTIVE: To determine results of diagnostic testing, including detection of nasal or frontal sinus fungal plaques, in dogs with nasal aspergillosis. DESIGN: Retrospective case series. ANIMALS: 46 dogs with nasal aspergillosis. PROCEDURES: Medical records were reviewed for information on computed tomographic findings; rhinoscopic findings, including whether fungal plaques were seen in the nasal cavity; results of frontal sinus trephination and sinuscopy, including whether fungal plaques were seen in the frontal sinus; and results of histologic examination of biopsy specimens. RESULTS: In 38 (83%) dogs, fungal plaques were seen in the nasal cavity during rhinoscopy, whereas in the remaining 8 (17%), fungal plaques were not seen in the nasal cavity but were seen in the frontal sinus. Duration of clinical signs, proportions of dogs in which the referring veterinarian had performed a nasal examination prior to referral, proportions of dogs with computed tomographic evidence of nasal cavity cavitation or sinus involvement, and proportions of dogs with rhinoscopic evidence of destructive rhinitis were not significantly different between dogs with nasal fungal plaques and dogs with fungal plaques only in the frontal sinus. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm that frontal sinus involvement is common in dogs with nasal aspergillosis and suggest that frontal sinus trephination and sinuscopy may aid in the diagnosis of aspergillosis in dogs, particularly dogs with rhinoscopic evidence of destructive rhinitis and computed tomographic evidence of sinus involvement that lack detectable fungal plaques in the nasal cavity.

Animals↗

Ultrasound assessment of angiogenesis in a matrigel model in rats.

Matrigel, a basement membrane extract, has been extensively used in in vivo angiogenesis. Contrast ultrasound imaging (CUI) of implanted Matrigel plugs with (+bFGF) and without basic fibroblast growth factor (-bFGF) was performed 7 and 14 d after implantation, followed by histologic analysis. Statistically significant differences between +bFGF and -bFGF plugs were apparent at d 7 in both plug size and contrast enhancement (both p < 0.05). Histopathology revealed differences in microvessel density (MVD) between +bFGF and -bFGF at d 7 and d 14. A significant correlation between MVD and both power Doppler contrast-enhanced area (r = 0.65, p < 0.05) and fraction of plug enhanced (r = 0.59, p < 0.05) was present. CUI of Matrigel plugs was shown to be a robust method for distinguishing between two different angiogenic states. Ultrasound measurements of blood flow in the plugs correlated with MVD, a histologic technique used to quantify tumor angiogenesis.

Animals↗

Contrast-assisted ultrasound for sentinel lymph node detection in spontaneously arising canine head and neck tumors.

OBJECTIVES: We sought to evaluate a minimally invasive contrast-assisted ultrasound (US) technique for sentinel lymph node (SLN) localization. METHODS: Microbubble contrast medium was injected into peritumoral tissues in 10 dogs with spontaneous head or neck tumors. Regional lymph nodes (LNs) were imaged up to 20 minutes after contrast administration using power Doppler US. Comparative lymphoscintigraphy studies were performed in all dogs by peritumoral injection of 99mTc-sulfur colloid administered around the primary lesion. RESULTS: US contrast enhancement of SLN revealed sentinel nodes and associated lymphatics in 8 of 10 dogs. In each instance in which contrast-enhanced LN was identified with US, a corresponding SLN was detected by lymphoscintigraphy. Multiple SLNs were present in 2 dogs. Regional lymph nodes were positive for metastasis in 1 dog and reactive in 9 dogs. CONCLUSIONS: Contrast-assisted US is effective in localizing SLN. This technique could reduce or eliminate many of the limitations of current SLN detection procedures.

Animals↗

Computed tomographic evaluation of canine radioulnar incongruence in vivo.

OBJECTIVE: To compare radioulnar incongruence (RUI) of normal canine elbows and elbows with arthroscopically confirmed medial compartment disease in vivo using systematic computed tomography (CT) measurements. STUDY DESIGN: Prospective comparison of RUI measurements in normal and dysplastic canine elbows. SAMPLE POPULATION: Right elbows of 25 medium-large breed, adult dogs with medial compartment disease and 9 medium-large breed, adult dogs with no elbow disease. METHODS: Transverse CT images of proximal radioulnar articulation were reformatted to dorsal and sagittal planes. RUI in 3 locations of the forelimb's medial coronoid was measured. Arthroscopy confirmed diagnosis of medial compartment disease in the diseased group. RUI measurements of the diseased and normal elbows were compared. RESULTS: Cumulative statistical analysis of RUI in all planes revealed no significant difference between the normal and abnormal elbows (P = .61). The abnormal elbows had negative mean RUI at the mid (P = .56) and cranial (P = .24) coronoid regions that were not significantly different from normal elbows and mean positive RUI at the base coronoid that was significantly greater than in normal elbows (P = .00082). CONCLUSION: Canine elbows with established medial compartment disease do not have significant RUI at the medial coronoid region at the time of diagnosis when compared with normal elbows. CLINICAL RELEVANCE: If RUI is a significant factor in the pathophysiology of medial compartment elbow disease in the dog, it does not appear to be present at the time of diagnosis of disease. Ulnar or radial osteotomies do not appear to be indicated for restoration of normal radioulnar articular surface alignment.

Analysis of Variance↗

The effect of size on the acoustic response of polymer-shelled contrast agents.

In this technical note, we study three polymer-shelled microbubble contrast agents manufactured by POINT Biomedical Corporation that have identical shell composition and mean volumetric diameters of 0.74 microm, 0.91 microm and 1.33 microm. We investigate the effect of agent size on the amplitude, frequency and probability of acoustic echoes received in response to five-cycle, 2.25-MHz pulses of varying pressure. We find that the amplitude and frequency response from the three agents is not significantly different. However, significant differences among the agents do exist in the probability of response to acoustic interrogation: at a pressure of 1.06 MPa, an echo from the 1.33 microm agent is 5 times as likely as an echo from the 0.91 microm agent and 18 times as likely as an echo from the 0.74 microm agent. We hypothesize that there exists an effective pressure-dependent threshold diameter above which single polymer-shelled agents respond to acoustic interrogation.

Contrast Media↗

Contrast-enhanced computed tomography and ultrasound for the evaluation of tumor blood flow.

OBJECTIVE: We evaluated implanted rat mammary adenocarcinoma tumors during a 5-week period using ultrasound, computed tomography (CT), and histology. MATERIALS AND METHODS: Contrast-enhanced ultrasound with a destruction-replenishment imaging scheme was used to derive estimates of blood volume and flow. These ultrasound-derived measures of microvascular physiology were compared with contrast-enhanced CT-derived measures of perfusion and vascular volume made by the Mullani-Gould formula and Patlak analysis, respectively. RESULTS: The tumor cross-sectional area and necrotic core cross-sectional area determined by the 3 methods were correlated (r>0.8, P<0.001, n=15). The spatial integral of perfusion estimated by CT correlated with the spatial integral of flow from ultrasound (P<0.05). The contrast-enhanced tumor area calculated from the ultrasound analysis was highly correlated with the contrast-enhanced area estimated by CT images (r=0.89, P<0.001, n=15). However, the fraction of the tumor area enhanced by the CT contrast agent was significantly larger than either the fraction enhanced by ultrasound contrast agent or than the viable area as estimated from histology slides. CONCLUSION: Destruction-replenishment ultrasound provides valuable information about the spatial distribution of blood flow and vascular volume in tumors and ultrasound analysis compares favorably with a validated contrast-enhanced CT method.

Adenocarcinoma↗

Comparison of myocardial contrast enhancement via cardiac magnetic resonance imaging in healthy cats and cats with hypertrophic cardiomyopathy.

OBJECTIVE: To quantify myocardial contrast enhancement (MCE) of the left ventricle (LV) by use of cardiac magnetic resonance imaging (CMRI) in healthy cats and cats with hypertrophic cardiomyopathy (HCM) and to compare MCE between the 2 groups. ANIMALS: 10 healthy cats and 26 Maine Coon cats with moderate to severe HCM but without clinical evidence of congestive heart failure. PROCEDURE: Anesthetized cats underwent gradient echo CMRI examination. Short-axis images of the LV were acquired before and 7 minutes after IV administration of gadolinium dimeglumine. Regions of interest were manually traced in the quadrants of 5 mid-LV slices acquired at end systole, and the MCE percentage was calculated from summed weight-averaged data from all slices. Doppler tissue imaging echocardiography was performed to measure the early diastolic myocardial velocity (Em) as an index of diastolic function. Three-way repeated-measures ANOVA was used to determine differences in MCE between cats with HCM and healthy cats. Simple linear regression was used to assess whether MCE was correlated with LV mass, LV mass index (LVMI), or Em. A Student t test was used to compare the SDs of the postcontrast myocardial signal intensity between the 2 groups. RESULTS: There was no difference in MCE between cats with HCM and healthy cats. There was no correlation of MCE with LV mass, LVMI, or Em. There was no difference in heterogeneity of signal intensities of LV myocardium between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Contrast-enhancement CMRI was not useful in detecting diffuse myocardial fibrosis in cats with HCM.

Animals↗

Quantitative evaluation of perfusion and permeability of peripheral tumors using contrast-enhanced computed tomography.

RATIONALE AND OBJECTIVES: Our purpose was to validate contrast-enhanced computed tomography (CECT)-derived quantitative measures of perfusion and permeability against gold standard techniques of fluorescent microspheres and Evan's Blue dye, respectively. MATERIALS AND METHODS: Normal and tumor-bearing (R3230AC) Fischer 344 rats were used. CECT perfusion measurements of normal and tumor tissue were compared with quantitative fluorescent microsphere perfusion measures. CECT permeability measurements from tumors were compared with semiquantitative Evan's Blue Dye permeability estimates. CT images were obtained precontrast and an imaging plane was selected. Serial, stationary images were obtained every 2 seconds for 2 minutes after intravenous bolus of iodinated contrast. Permeability and perfusion were measured by applying Patlak analysis to time-density data from normal tissue or tumor and femoral artery. RESULTS: There was good correlation between fluorescent microsphere and CECT measurements of perfusion (r2 = 0.681, P << 0.001) and between Evan's Blue Dye and CECT measurements of permeability (r2 = 0.873, P = 0.0007). CONCLUSIONS: CECT provides useful, quantifiable measures of perfusion and permeability in peripheral tumors.

Animals↗

Spinal cord effects from lumbar myelographic injection technique in the dog.

To characterize spinal cord effects of needle placement using lumbar puncture myelography technique, lumbar puncture was performed in 5 dogs and computed tomography images of the spinal column were acquired in the transverse plane at the level of the puncture site after contrast injection and both before and after needle removal. The spinal cords were punctured during needle placement and parenchymal contrast enhancement was present in 4 of 5 dogs. Although no dogs exhibited overt neurological abnormalities following computed tomographic imaging, hemorrhage, gliosis and axonal degeneration were confirmed microscopically in all subjects. These results suggest that spinal cord morbidity is induced when lumbar myelography is performed using currently accepted technique.

Animals↗

Correlation of helical and incremental high-resolution thin-section computed tomographic and histomorphometric quantitative evaluation of an acute inflammatory response of lungs in dogs.

OBJECTIVE: To compare quantitative densitometric computed tomography (CT), morphometric, and histologic data of normal lungs in dogs with similar parameters obtained after induction of an acute inflammatory response and determine whether CT densitometry correlated with histopathologic changes. ANIMALS: 6 healthy adult dogs. PROCEDURE: After initial CT, 1 mL of 0.1 M hydrochloric acid (HCI) and 3 mL of autologous blood were instilled into the right middle (RM) and caudal segment of the left cranial (LCCd) lung lobes, respectively. Immediately and 24 hours after instillation, CT was repeated. At 24 hours, dogs were euthanatized and lungs were fixed and sampled for morphometric and histologic evaluation. The CT data were compared with lung morphology and morphometry by use of unpaired t tests. Comparison with lungs from control dogs was performed using Spearman rank correlation coefficients. RESULT: Mean Hounsfield units (HU) from control and baseline HU from experimental dogs were identical. Immediately after instillation of HCI or blood, there was increased attenuation in both lobes. Autologous blood initially induced severe changes that almost completely resolved at 24 hours; HCI induced severe changes at 24 hours. Significant increases in percentage of parenchymal airspace and alveolar diameter resulted in decreased surface area-to-volume ratio in lobes receiving HCl. Histologic scores were significantly higher in the RM lobe, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: Computed tomography attenuation correlated well with histomorphometry and histologic findings in this model. Lung lesions after autologous blood were transient and of limited severity. Lesions induced by HCl were severe; alterations in morphometric and histologic parameters were reflected in CT attenuation measurements.

Acute-Phase Reaction↗

Response of induced bone defects in horses to collagen matrix containing the human parathyroid hormone gene.

OBJECTIVE: To determine whether human parathyroid hormone (hPTH) gene in collagen matrix could safely promote bone formation in diaphyseal or subchondral bones of horses. ANIMALS: 8 clinically normal adult horses. PROCEDURE: Amount, rate, and quality of bone healing for 13 weeks were determined by use of radiography, quantitative computed tomography, and histomorphometric analysis. Diaphyseal cortex and subchondral bone defects of metacarpi were filled with hPTH(1-34) gene-activated matrix (GAM) or remained untreated. Joints were assessed on the basis of circumference, synovial fluid analysis, pain on flexion, lameness, and gross and histologic examination. RESULTS: Bone volume index was greater for cortical defects treated with hPTH(1-34) GAM, compared with untreated defects. Bone production in cortical defects treated with hPTH(1-34) GAM positively correlated with native bone formation in untreated defects. In contrast, less bone was detected in hPTH(1-34) GAM-treated subchondral bone defects, compared with untreated defects, and histology confirmed poorer healing and residual collagen sponge. CONCLUSIONS AND CLINICAL RELEVANCE: Use of hPTH(1-34) GAM induced greater total bone, specifically periosteal bone, after 13 weeks of healing in cortical defects of horses. The hPTH(1-34) GAM impeded healing of subchondral bone but was biocompatible with joint tissues. Promotion of periosteal bone formation may be beneficial for healing of cortical fractures in horses, but the delay in onset of bone formation may negate benefits. The hPTH(1-34) GAM used in this study should not be placed in articular subchondral bone defects, but contact with articular surfaces is unlikely to cause short-term adverse effects.

Analysis of Variance↗

Use of computed tomography angiography to evaluate the vascular anatomy of the distal portion of the forelimb of horses.

OBJECTIVE: To provide a detailed description of the vascular anatomy of the distal portion of the forelimbs of horses by use of computed tomography angiography (CTA). SAMPLE POPULATION: 6 forelimbs of 5 horses and 1 forelimb from an equine cadaver; none of the horses had orthopedic or vascular disease. PROCEDURE: Horses were anesthetized and CTA was conducted on the dependent forelimb. A catheter was inserted in the median artery, and contrast medium was infused at a rate of 3 mL/s. A computed tomography (CT) scanner was used to obtain contiguous slices from the region of the proximal sesamoid bones to the toe. All horses were allowed to recover from anesthesia. To help identify vessel patterns in the distal portion of the forelimb, the median artery and lateral palmar digital vein of a heparinized forelimb obtained from an equine cadaver were infused with red and blue polymethylmethacrylate and the distal portion of that forelimb was then sectioned to correspond to CTA images. RESULTS: Vessel patterns in CTA images matched vascular anatomic structures of the cadaver forelimb and were consistent with published anatomic structures. Major and minor vessels were consistently visible in CTA images of all horses. There were no complications reported in any horses. CONCLUSIONS AND CLINICAL RELEVANCE: Use of CTA provided a highly detailed depiction of the vasculature of the distal portion of the equine forelimb. This was a safe technique and should be useful in the evaluation of the blood supply to the distal portion of the forelimb.

Angiography↗

Contrast-enhanced US of microcirculation of superficially implanted tumors in rats.

PURPOSE: To determine the ability of contrast material-enhanced ultrasonography (US) to assess replenishment time in a rat kidney and adenocarcinoma tumor model. MATERIALS AND METHODS: Mammary adenocarcinoma cells were implanted into the subcutaneous tissues of the flank of 11 rats. Resultant tumors were imaged serially with contrast-enhanced US and compared with images of the rat kidney, a highly perfused normal organ. The US acquisition and processing methods yield images of perfused tumor regions and the times required to achieve 80% replenishment. Findings at contrast-enhanced computed tomography (CT) and light microscopy of hematoxylin-eosin-stained tumor tissue were compared. Paired Student t test was performed to compare the accuracy of US with that of histologic examination and CT in the detection of viable tumor regions. RESULTS: Replenishment of the kidney cortex microvasculature requires 1-5 seconds compared with a replenishment time of 6-14 seconds in tumors. Over the time course of tumor growth, the mean perfusion time becomes progressively longer, and a wider range of perfusion times is detected. Comparison of findings at US, CT, and histologic examination suggested that all three methods yield correlated estimates of the percentage of viable perfused tumor cells. Results of the t test suggested that the viable tumor percentages observed at US are not significantly different from those observed at CT and histologic examination (US vs CT, P =.92; US vs histologic examination, P =.94). CONCLUSION: Repeated measurements of microvascular flow rate can be accomplished in a rat animal model with a minimally invasive technique.

Adenocarcinoma↗

Improved detection of metastases on magnetic resonance images by digital tissue recognition: validation using VX-2 tumor in the rabbit.

PURPOSE: To evaluate the ability of a prototype digital tissue recognition (DTR) system to improve the accuracy of detection of metastases on magnetic resonance (MR) images in the rabbit VX-2 tumor model. MATERIALS AND METHODS: Multiple MR imaging (MRI) sequences, including pre-contrast and post-contrast enhanced T1-weighted, T2-weighted, proton-density, and fast short inversion time inversion recovery (FSTIR), were acquired for six rabbits implanted with VX-2 adenocarcinoma. For each rabbit, DTR used the MR intensity characteristics of a known tumor site to highlight other areas suspicious for tumor. Three independent veterinary radiologists with extensive experience in animal MRI interpreted the images for tumor both without and with the results of DTR. The conventional and DTR-assisted interpretations were compared to pathology. RESULTS: Using DTR, the radiologists found an average of 13.2% more true positive sites with a 10.3% reduction in false positives compared to unassisted interpretation. The improvement for the radiologists was statistically significant (McNemar's test, P = 0.0004). The agreement between radiologists using DTR was consistently higher than for their conventional interpretations (kappa statistic). CONCLUSION: Compared with conventional interpretation of MR images, the use of DTR provided a statistically significant improvement in the accuracy of locating more and smaller sites of tumor. This improvement was achieved without the benefit of post-contrast images.

Adenocarcinoma↗

Progressive swelling, hyperkeratosis, and fibrosis of distal limbs in Clydesdales, Shires, and Belgian draft horses, suggestive of primary lymphedema.

BACKGROUND: A condition characterized by progressive swelling, hyperkeratosis, and fibrosis of the distal limbs has been recognized in Shire, Clydesdale, and Belgian draft horses. This chronic progressive disease starts at an early age, progresses throughout the life of the horse, and often ends in disfigurement and disability of the limbs that inevitably leads to the horse's premature death. This study was undertaken to better characterize this disease. METHODS AND RESULTS: Six affected horses were donated for diagnostic workup. A detailed clinical, radiologic, gross, and histologic description is given in this report. The lesions in the limb consisted of progressive development of thick-walled lymphatics, associated with chronic dermal edema, inflammation, fibrosis, neovascularization, and elastin degeneration. In the end stages, arteriosclerosis and fibrosed veins were also present. The clinical signs and pathologic changes in this disease closely resemble the human condition of elephantiasis nostras verrucosa, a state in which chronic lymphedema plays a pivotal pathogenic role.

Angiography↗

Correlation of helical and incremental high-resolution thin-section computed tomographic imaging with histomorphometric quantitative evaluation of lungs in dogs.

OBJECTIVE: To develop protocols for helical computed tomography (CT) and axial high-resolution CT (HRCT) of lungs and correlate densitometric CT values with morphometric and histologic data for normal pulmonary tissue in dogs. ANIMALS: 8 healthy adult dogs. PROCEDURE: 2 dogs were used to establish a protocol for helical CT and HRCT of lungs. Six dogs were used to acquire densitometric CT data regarding normal lungs. After the dogs were euthanatized, their lungs were fixed and sampled for morphometric and histologic evaluation. Four CT acquisitions were compared by means of paired t tests. RESULTS: For normal lung tissue of dogs, mean densitometric CT value obtained during helical CT scans reconstructed in a sharp algorithm was -846 Hounsfield units. Values obtained via helical CT or HRCT acquisitions and reconstructed with sharp or standard algorithms did not differ significantly. Morphometric analysis was used to determine the proportion of lung parenchymal (82%) and non-parenchymal tissue (18%). Alveolar size, estimated by mean linear intercept, was approximately 172 microm, and alveolar surface area-to-volume ratio was 0.024 to 0.026 microm(-1). Histologic evaluation confirmed the presence of normal lung tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Correlation of densitometric CT data with morphometric and histologic findings and the establishment of helical CT and HRCT protocols were attained; clinical use of this information may facilitate investigation of pulmonary disease in dogs. Sharp helical CT acquisitions were preferred because of better lung parenchyma detail and rapid image acquisitions, compared with HRCT.

Animals↗

Sentinel node detection using contrast-enhanced power Doppler ultrasound lymphography.

RATIONALE AND OBJECTIVES: To establish the feasibility of using contrast-enhanced interstitial ultrasound (US) lymphography as an alternative to current sentinel node detection methods. METHODS: Aqueous US contrast microbubble suspensions of varying diameter were evaluated in vitro to characterize response to insonation. Contrast media were then injected subcutaneously into the distal extremities of 11 normal dogs to target the cervical and popliteal lymph nodes (nodes, n = 40). First-order (sentinel) lymph nodes and second-order sublumbar nodes were imaged intermittently from 0 to at least 120 minutes following contrast injection using continuous power Doppler mode. Lymphoscintigraphy studies were performed on 4 dogs to verify lymphatic drainage patterns and sentinel lymph nodes. RESULTS: Contrast enhancement occurred in 34/40 (85%) sentinel nodes overall and in 30/32 (94%) nodes when submicron or near-micron diameter bubble formulations were used. In many instances, enhancement persisted throughout the imaging period. Contrast response was most pronounced using a high mechanical index and tissue artifact was reduced or eliminated when using a high pulse repetition frequency. CONCLUSIONS: Contrast-enhanced interstitial US lymphography could serve as an alternative to current sentinel node detection methods. Preliminary findings suggest that submicron or near-micron-diameter bubbles may be suitable for lymphatic imaging applications.

Animals↗

Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect.

Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24(-/-)) have indicated a role for Zmpste24 in the processing of CAAX-type prenylated proteins. Here, we report the pathologic consequences of Zmpste24 deficiency in mice. Zmpste24(-/-) mice gain weight slowly, appear malnourished, and exhibit progressive hair loss. The most striking pathologic phenotype is multiple spontaneous bone fractures-akin to those occurring in mouse models of osteogenesis imperfecta. Cortical and trabecular bone volumes are significantly reduced in Zmpste24(-/-) mice. Zmpste24(-/-) mice also manifested muscle weakness in the lower and upper extremities, resembling mice lacking the farnesylated CAAX protein prelamin A. Prelamin A processing was defective both in fibroblasts lacking Zmpste24 and in fibroblasts lacking the CAAX carboxyl methyltransferase Icmt but was normal in fibroblasts lacking the CAAX endoprotease Rce1. Muscle weakness in Zmpste24(-/-) mice can be reasonably ascribed to defective processing of prelamin A, but the brittle bone phenotype suggests a broader role for Zmpste24 in mammalian biology.

Age Factors↗