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A permanent stoma is an unintended consequence that cannot be avoided completely after intersphincteric resection for ultralow rectal cancer. Unfortunately, its incidence and risk factors have been poorly defined.The objective was to determine the cumulative incidence and risk factors of permanent stoma after intersphincteric resection for ultralow rectal cancer.This study was a retrospective analysis of prospectively collected data.This study was conducted at a colorectal surgery referral center.A total of 185 consecutive patients who underwent intersphincteric resection with diverting ileostomy from 2011 to 2019 were included.The primary outcome was the incidence of and risk factors for the permanent stoma. The secondary outcome included differences in stoma formation between patients with partial, subtotal, and total intersphincteric resection.After a median follow-up of 40 months (range, 6-107 months), 26 of 185 patients eventually required a permanent stoma, accounting for a 5-year cumulative incidence of 17.4%. The causes of permanent stoma were anastomotic morbidity (46.2%, 12/26), local recurrence (19.2%, 5/26), distant metastasis (19.2%, 5/26), fecal incontinence (3.8%, 1/26), perioperative mortality (3.8%, 1/26), patients' refusal (3.8%, 1/26), and poor general condition (3.8%, 1/26). Although the incidence of permanent stoma was significantly different between the intersphincteric resection groups (partial vs subtotal vs total: 8.3% vs 20% vs 25.8%, p = 0.02), it was not an independent predictor of stoma formation. Multivariate analysis demonstrated that anastomotic leakage (OR = 5.29; p = 0.001) and anastomotic stricture (OR = 5.13; p = 0.002) were independently predictive of permanent stoma.This study was limited by its retrospective nature and single-center data.The 5-year cumulative incidence of permanent stoma was 17.4%. Anastomotic complications were identified as risk factors. Patients should be informed of the risks and benefits when contemplating the ultimate sphincter-sparing surgery. It might be preferable to decrease the probability of permanent stoma by further minimizing anastomotic complications. See Video Abstract at http://links.lww.com/DCR/B704.ANTECEDENTES:La necesidad de efectuar un estoma permanente es la consecuencia no intencional e inevitable por completo después de una resección interesfintérica en presencia de un cáncer rectal ultra bajo. Desafortunadamente, la incidencia y los factores de riesgo se han definido en una forma limitada.OBJETIVO:El objetivo fue determinar la incidencia acumulada y los factores de riesgo para la necesidad de efectuar un estoma permanente después de la resección intersfintérica de un cáncer rectal ultra bajo.DISEÑO:El presente estudio es un análisis retrospectivo de la información obtenida.ESCENARIO:Centro de referencia de cirugía colo-rectal.PACIENTES:Se incluyeron un total de 185 pacientes consecutivos que se sometieron a resección intersfintérica de un cáncer rectal ultra bajo con ileostomía de derivación de 2011 a 2019.MEDICION DE RESULTADOS:El resultado principal fue la identificación de la incidencia y los factores de riesgo para la presencia de un estoma permanente. En forma secundaria se describieron los resultados de las diferentes técnicas de la formación de un estoma entre los pacientes con resección interesfintérica parcial, subtotal o total.RESULTADOS:Posterior a una media de seguimiento de cuarenta meses (rango de 6 a 107), 26 de 185 pacientes requirieron en forma eventual un estoma permanente, lo que equivale a una incidencia acumulada a cinco años de 17.4 %. Las causas para dejar un estoma permanente fueron morbilidad de la anastomosis (46.2%, 12/26), recurrencia local (19.2%, 5/26), metástasis a distancia (19.2%, 5/26), incontinencia fecal (3.8%, 1/26), mortalidad perioperatoria (3.8%, 1/26), rechazo del paciente (3.8%, 1/26), y malas condiciones generales (3.8%, 1/26). Aunque la incidencia de un estoma permanente fue significativamente diferente entre los grupos de resección interesfintérica (parcial vs subtotal vs total: 8.3% vs 20% vs 25.8%, p = 0.02), no se consideró un factor predictor independiente para la formación de estoma. En el análisis multivariado se demostró que la fuga anatomótica (OR = 5.29; p = 0.001) y la estenosis anastomótica (OR = 5.13; p = 0.002) fueron factores independientes para predecir la necesidad de un estoma permanente.LIMITACIONES:La naturaleza retrospectiva del estudio y la información proveniente de un solo centro.CONCLUSIONES:La incidencia acumulada a cinco años de estoma permantente fue de 17.4%. Se consideran a las complicaciones anastomóticas como factores de riesgo. Los pacientes deberán ser informados de los riesgos y beneficios cuando se considere la posibilidad de efectuar una cirugía preservadora de esfínteres finalmente. Puede ser preferible disminuir la probabilidad de dejar un estoma permanente tratando de minimizar la posibilidad de complicaciones de la anastomosis. Consulte Video Resumen en http://links.lww.com/DCR/B704.

Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug-releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug-loaded nanoparticles into microgel building blocks via microfluidic manufacturing. By modulating nanoparticle hydrophilicity and pregel solution viscosity, drugMAP building blocks are generated with consistent and homogeneous encapsulation of nanoparticles. In addition, the complementary effects of forskolin (F) and Repsox (R) on the functional modulations of cardiomyocytes, fibroblasts, and endothelial cells in vitro are demonstrated. After that, both hydrophobic drugs (F and R) are loaded into drugMAP to generate FR/drugMAP for MI therapy in a rat model. The intramyocardial injection of MAP gel improves left ventricular functions, which are further enhanced by FR/drugMAP treatment with increased angiogenesis and reduced fibrosis and inflammatory response. This drugMAP platform represents a new generation of microgel particles for MI therapy and will have broad applications in regenerative medicine and disease therapy.

Based on the explicit dynamic analysis method, the finite element models of successive shots and multiple shots for shot peening process are established by using LS-DYNA software.The simulations of the elastic-plastic dynamic process of shots impacting on a metallic target during shot peening process were accomplished. For Al2024-T3 alloy plate, the surface roughness induced by shot peening is studied and the effect of overlapping on the general trend is evaluated.The analysis results show that the surface roughness increases rapidly at the initial stage of shot peening and forms micro-scale pits. With the increase of the coverage, the surface deformation increased slowly when the surface coverage reached 100%.

This study aims to investigate the influence of high linear energy transfer (LET) heavy ion (12C6+) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion (12C6+) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion (12C6+). High LET heavy ion (12C6+) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion (12C6+) presented special advantages in terms of treating malignant melanoma. Impact statement Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate. In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to overcome its lower sensitivity to radiation. This study can provide theoretical basis for clinical trials, in which malignant melanoma is treated by heavy ion (12C6+), in order to accurately determine the clinical efficacy of heavy ion therapy. Clinical applications has revealed that local tumor control rate is high when heavy ion is used to treat malignant melanoma, indicating that heavy ion is an important direction in treating melanoma in the future.

To assess the ability of dual-energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double-contrast enhanced scans using iodinated intravenous contrast and experimental enteric non-iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (-100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30-44% and 36-45%, both p

Background and aims: Synchronous liver metastasis (SLM) remains a significant problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte growth factor (HGF) and Met plays an important role in cancer invasion and metastasis and is being developed to be targeted drugs. We aimed to investigate the role of HGF/Met in SLM based on a case-matched study and comparison between primary tumors and matched metastases. Methods: A group of 30 patients with SLM and other two groups of patients without SLM in a hospital database were collected. They were matched into according to clinicopathological factors. 81 patients were included in the study. Their tissues of primary colorectal cancers, lymph nodes and liver metastases were collected to detect HGF and Met expression by immunohistochemistry and RT-PCR. Results: Expression of HGF and Met at the protein level and the RNA level in primary CRCs with SLM were significantly higher than that in primary colorectal carcinomas without liver metastases (all P value0.05). Comparison their expression between primary tumors and matched metastases, major concordance and minor difference existed. Conclusions: HGF and Met may exert functions in the development of SLM when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, further indicating their roles and potential values for a subtype of colorectal cancer metastasis. Major concordance and minor difference exist between primary tumors and matched metastases, which further provides evidence for evaluating the response to their inhibitors based on primary tumors or metastases.

Purpose: Semi-quantitative, static positron emission tomography (PET) has been used to perform an initial approach to the assessment of [13N]-ammonia perfusion studies aimed to elucidating the effect of injecting human embryonic stem cell-derived (hES) hemangioblasts on infarcted rat hearts. Procedures: Female NIH nude rats underwent occlusion of the left anterior descending coronary artery for 30 min before reperfusion. Either one million hES-derived hemangioblasts (n=5) or control media (n=4) were injected into the site of the infarct 1 day post-myocardial infarction (MI) under high-resolution echocardiography guidance. PET imaging was performed 6 weeks after MI induction, and uptake polar maps were created by sampling the left ventricle at equidistant slices from the base to the apex and measuring the average myocardium value at three contiguous voxels to minimize partial volume effects. Statistical comparison between treatment and control groups was done with a Mann–Whitney U test. Results: Myocardium uptake ratios for treated and untreated subjects show statistically significant difference (98% certainty). Conclusions: The straightforward procedure described here (similar to those commonly used in clinical routine) was sufficient to yield statistically significant perfusion differences between the treated and untreated animals despite the small sample size. This work was supported in part by the RETICRECAVA program, Ministerio de Ciencia e Innovación, Spain. En prensa

This task is based on the control of the MCU. In order to make it work, the first and foremost thing is to configure the interface among the MCU, display device and the wireless communication device with reason. In detail, the hardware design concludes the MCU control system, display circuit as well as the design of the wireless one. As for the software design, there are the initialization of the MCU and the display component. The programmer for the control of the display part and wireless part are also concluded.

Human antibodies targeting all subtypes of mesothelioma could be useful to image and treat this deadly disease. Here we report tumor targeting of a novel internalizing human single chain antibody fragment (scFv) labeled with 99mTc (99mTc-M40) in murine models of mesothelioma of both epithelioid (M28) and sarcomatoid (VAMT-1) origins. 99mTc-M40 was taken up rapidly and specifically by both subtype tumor cells in vitro, with 68% to 92% internalized within 1 hour. The specificity of binding was evidenced by blocking (up to 95%) with 10-fold excess of unlabeled M40. In animal studies, tumors of both subtypes were clearly visualized by SPECT/CT as early as 1 hour postinjection of 99mTc-M40. Tumor uptake measured as percent of injected dose per gram tissue (%ID/g) at 3 hours was 4.38 and 5.84 for M28 and VAMT-1 tumors, respectively, significantly greater than all organs or tissues studied (liver, 2.62%ID/g; other organs or tissues

The prognosis for patients diagnosed with mesothelioma is generally poor, and currently available treatments are usually ineffective. Therapies that specifically target tumor cells hold much promise for the treatment of cancers that are resistant to current approaches. We have previously selected phage antibody display libraries on mesothelioma cell lines to identify a panel of internalizing human single chain (scFv) antibodies that target mesothelioma-associated, clinically represented cell surface antigens and further exploited the internalizing function of these scFvs to specifically deliver lethal doses of liposome-encapsulated small molecule drugs to both epithelioid and sarcomatous subtypes of mesothelioma cells. Here, we report the identification of MCAM/MUC18/CD146 as the surface antigen bound by one of the mesothelioma-targeting scFvs using a novel cloning strategy based on yeast surface human proteome display. Immunohistochemical analysis of mesothelioma tissue microarrays confirmed that MCAM is widely expressed by both epithelioid and sarcomatous types of mesothelioma tumor cells in situ but not by normal mesothelial cells. In addition, quantum dot-labeled anti-MCAM scFv targets primary meosthelioma cells in tumor fragment spheroids cultured ex vivo. As the first step in evaluating the therapeutic potential of MCAM-targeting antibodies, we performed single-photon emission computed tomography studies using the anti-MCAM scFv and found that it recognizes mesothelioma organotypic xenografts in vivo. The combination of phage antibody library selection on tumor cells and rapid target antigen identification by screening the yeast surface-displayed human proteome could be a powerful method for mapping the targetable tumor cell surface epitope space. [Cancer Res 2009;69(4):1570–7]

Immune responses that occur in the context of human infectious and inflammatory diseases are usually studied by sampling cells from peripheral blood, from biopsies, or by end-point harvests at necropsy. These approaches are likely to yield information that is incomplete and/or non-representative. Here, we report the development and validation of a non-invasive method to localize and to quantitate the disposition of specific subpopulations of cells in vivo. In a murine model of dextran sulfate sodium (DSS)-induced colitis, CD4+ T cells were visualized in the colon by single photon emission computed tomography (SPECT-CT) after injection of monoclonal, non-depleting, indium-111 (111In) labeled anti-CD4+ antibodies. The SPECT-CT colon uptake ratio (CUR) was found to correlate (p

In addition to their role in protecting the ends of chromosomes, telomeres also influence the expression of adjacent genes, a process called telomere-position effect. We previously reported that the neo and HSV-tk transgenes located adjacent to telomeres in mouse embryonic stem cells are initially expressed at low levels and then become gradually silenced upon passage in culture through a process involving DNA methylation. We also reported extensive DNA methylation in these telomeric transgenes in three different tissues isolated from mice generated from one of these embryonic stem cell clones. In the present study, we demonstrate that embryo fibroblasts isolated from two different mouse strains show extensive DNA methylation and silencing of the telomeric transgenes. Consistent with this observation, we also demonstrate little or no detectable expression of the HSV-tk telomeric transgene in somatic tissues using whole body imaging. In contrast, both telomeric transgenes are expressed at low levels and have little DNA methylation in embryonic stem cell lines isolated from these same mouse strains. Our results demonstrate that telomere-position effect in mammalian cells can be observed either as a low level of expression in embryonic stem cells in the preimplantation embryo or as complete silencing and DNA methylation in differentiated cells and somatic tissues. This pattern of expression of the telomeric transgenes demonstrates that subtelomeric regions, like much of the genome, are epigenetically reprogrammed in the preimplantation embryo, a process that has been proposed to be important in early embryonic development. Disclosure of potential conflicts of interest is found at the end of this article.

We evaluated methods of imaging rat models of stroke in vivo using a single photon emission computed tomography (SPECT) system dedicated to small animal imaging (X-SPECT, Gamma Medica-Ideas, Northridge, CA). An animal model of ischemic stroke was developed for in vivo SPECT/CT imaging using the middle cerebral artery occlusion (MCAO) technique. The presence of cerebral ischemia was verified in ex vivo studies using triphenyltetrazolium chloride (TTC) staining. In vivo radionuclide imaging of cerebral blood flow was performed in rats following MCAO using dynamic planar imaging of 99mTc-exametazime with parallel hole collimation. This was followed immediately by in vivo radionuclide imaging of cerebral blood flow with 99mTc-exametazime in the same animals using 1-mm pinhole SPECT. Correlated computed tomography imaging was performed to localize radiopharmaceutical uptake. The animals were allowed to recover and ex vivo autoradiography was performed with separate administration of 99mTc-exametazime. Time activity curve of 99mTc-exametazime showed that the radiopharmaceutical uptake could be maintained for over 9 min. The activity would be expected to be relatively stable for a much longer period, although the data were only obtained for 9 min. TTC staining revealed sizable infarcts by visual observation of inexistence of TTC stain in infracted tissues of MCAO rat brains. In vivo SPECT imaging showed cerebral blood flow deficit in the MCAO model, and the in vivo imaging result was confirmed with ex vivo autoradiography. We have demonstrated a capability of imaging regions of cerebral blood flow deficit in MCAO rat brains in vivo using a pinhole SPECT dedicated to small animal imaging.

To assess the ability of dual-energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double-contrast enhanced scans using iodinated intravenous contrast and experimental enteric non-iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (-100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30-44% and 36-45%, both p 0.001) higher for double-contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double-contrast DECT was scored 29 and 35 percentage points (95% CI 20-35% and 33-39%, both p 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double-contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15-31% and 28-33%, both p 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double-contrast DECT with iodinated intravenous and either tantalum- or tungsten-based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John WileySons, Ltd.

ObjectivesAlthough transgenic mice have emerged as powerful experimental models of cardiovascular disease, methods for in vivo phenotypic assessment and characterization remain limited, motivating the development of new instruments for biologic measurement.BackgroundWe have developed a single-photon emission computed tomography system with a pinhole collimator (pinhole SPECT) for high-resolution cardiovascular imaging of mice. In this study, we describe a protocol for myocardial perfusion imaging of mice using technetium-99m (99mTc)-sestamibi and demonstrate the feasibility for measurement of perfusion defect size from pinhole SPECT images.MethodsMice were anesthetized and injected with 370 MBq (10 mCi) of 99mTc-sestamibi. Tomographic projection images were acquired by rotating each mouse in a vertical axis in front of a stationary clinical scintillation camera equipped with a pinhole collimator. BALB/c mice (n = 15) were imaged after the permanent ligation of the left anterior descending coronary artery. The resulting defect size was measured from circumferential profiles of short-axis images. After imaging, the hearts were excised and sectioned to obtain ultra-high resolution digital autoradiographs of 99mTc-sestamibi, from which the actual infarct size was determined.ResultsReconstructed image quality was equivalent to that obtained for clinical myocardial perfusion imaging. Linear regression analysis produced a correlation coefficient of 0.83 (p < 0.001) between the measured and actual values of the defect size.ConclusionsThese results demonstrate that myocardial perfusion can be characterized qualitatively and quantitatively in mice using pinhole SPECT.

Background and Purpose— Numerous studies indicate that mild hypothermia provides substantial neuroprotection. However, current systems transfer insufficient heat to rapidly vary core temperature. We thus evaluated the safety and efficacy of endovascular cooling and rewarming for the induction and reversal of hypothermia. Methods— In 10 anesthetized pigs (weight, 66±2 kg), a heat-exchange balloon catheter was inserted into the inferior vena cava and used to cool to a core temperature of 32°C and then rewarm to normothermia. Control animals had 38°C saline infused. Venous blood was sampled before, during, and after cooling. Three animals in each group were killed 1 week later, and the lungs and inferior vena cava were removed for gross and microscopic examination. In 5 additional animals, cardiac output was measured during cooling to 32°C. Results— Body temperature in the hypothermic animals decreased at a rate of 4.5±0.4°C/h. Animals were subsequently rewarmed to 36.0±0.04°C at 2.5±0.2°C/h. There was no difference in heart rate between hypothermic and control animals, whereas systolic pressure decreased during cooling. Cardiac output was well maintained during cooling. There were no thermal effects on blood elements or blood vessels. Conclusions— The endovascular heat-exchange system effectively cooled and rewarmed pigs with large thermal mass without producing any adverse effects on blood elements, blood vessel integrity, or cardiovascular function.

Mild hypothermia reduces myocardial infarct size in small animals; however, the extent of myocardial protection in large animals with greater thermal mass remains unknown. We evaluated the effects of mild endovascular cooling on myocardial temperature, infarct size, and cardiac output in 60- to 80-kg isoflurane-anesthetized pigs. We occluded the left anterior descending coronary artery for 60 min, followed by reperfusion for 3 h. An endovascular heat-exchange catheter was used to either lower core body temperature to 34°C ( n = 11) or maintain temperature at 38°C ( n = 11). Additional studies assessed myocardial viability and microvascular perfusion with99mTc-sestamibi autoradiography. Endovascular cooling reduced infarct size compared with normothermia (9 ± 6% vs. 45 ± 8% of the area at risk; P < 0.001), whereas the area at risk was comparable (19 ± 3% vs. 20 ± 7%; P = 0.65). Salvaged myocardium showed normal sestamibi uptake, confirming intact microvascular flow and myocyte viability. Cardiac output was maintained in hypothermic hearts because of an increase in stroke volume, despite a decrease in heart rate. Mild endovascular cooling to 34°C lowers myocardial temperature sufficiently in human-sized hearts to cause a substantial cardioprotective effect, preserve microvascular flow, and maintain cardiac output.

The authors have developed a single photon emission computed tomography (SPECT) technique for high resolution radiotracer imaging of mice where the object is rotated instead of the scintillation camera. The system uses a 21 cm focal length pinhole collimator with a 0.5 mm diameter aperture, resulting in magnification ranging from 7 to 10 and acquisition times from 60 to 90 minutes. This method employs a plastic mouse-holding tube designed to address specific problems associated with pinhole SPECT, including low count rates and correction for shift of the center of rotation. Images of a novel "mouse heart" phantom demonstrated good image quality, uniformity, and spatial resolution. A /sup 99m/Tc-sestamibi scan of a normal mouse, electrocardiogram-gated at over 400 beats per minute, allowed assessment of regional myocardial perfusion and evaluation of ventricular wall motion. An ungated perfusion scan produced images with millimeter spatial resolution and quality comparable to human images, allowing the visualization of the left and right ventricular myocardium.

To estimate and compare the fractional distribution volume (fDV) of gadodiamide injection and technetium 99m-diethylenetriaminepentaacetic acid (DTPA) in the reperfused myocardium of rat hearts subjected to various durations of ischemia.Magnetic resonance (MR) imaging and autoradiography were performed in rats subjected to 20, 30, 40, or 60 minutes of regional ischemia followed by 1 hour of reperfusion. The fDVs of gadodiamide injection and (99m)Tc-DTPA were measured and compared by using inversion-recovery echo-planar imaging and autoradiographic phosphor imaging, respectively.The mean fDV of both tracers (gadodiamide and (99m)Tc-DTPA) in normal myocardium was 18% +/- 1, whereas that in the entire area at risk increased significantly (P.05) with 20, 30, 40, and 60 minutes of ischemia to 32% +/- 1, 57% +/- 4, 66% +/- 2, and 68% +/- 2, respectively. The fDV was significantly (P.05) greater in the core of infarction-78% +/- 4, 89% +/- 5, and 88% +/- 5 with 30, 40, and 60 minutes of ischemia, respectively-than in the normal myocardium or in the area at risk.The fDV of MR contrast material in the periinfarcted rim was significantly (P. 05) greater than that in the normal myocardium, but significantly less than that in the core of infarcted myocardium.

Background —Heterogeneity of sympathetic innervation is thought to contribute to the potential for fatal arrhythmia. However, little is known about the effects of heterogeneous innervation on repolarization. Methods and Results —To assess this relationship, we measured activation recovery intervals (ARIs) from 64 epicardial sites in 11 rabbits studied 2 weeks after regional denervation produced by phenol and 4 sham-operated rabbits. ARI results were compared with the distribution of sympathetic innervation measured from 3D reconstructions of serial autoradiographs of [ 125 I]metaiodobenzylguanidine and 99m Tc-sestamibi. ARIs were recorded during baseline sinus rhythm, norepinephrine (NE) infusion (0.1 μg · kg −1 · min −1 ), and left stellate ganglion stimulation (SS). NE shortened ARI in 98% of electrodes in the denervated region. The degree of ARI shortening and dispersion increased ( P P P Conclusions —The magnitude and dispersion of local repolarization responses are related to the severity of denervation, as well as the type of stimulation: neural (SS) versus humoral (NE). The differences may relate to the concentration of NE released.

Standard radionuclide imaging systems are of limited use due to their inability to resolve structures in small animals that represent an increasingly important model for the study of cardiovascular disease. The authors are developing an imaging system incorporating a scintillation camera with a pinhole collimator to acquire cardiac gated images of the mouse heart. Through a simulation study, the authors found that the effective diameter of the pinhole was unaffected by the scatter component of photon penetration through the pinhole insert. The authors have performed a myocardial perfusion study with 0.68 FWHM resolution on a normal 25 gram mouse gated at over 400 beats per minute. The authors have demonstrated that it is possible to obtain cardiac-gated, myocardial perfusion images of mice at submillimeter spatial resolution.

PurposeTo compare the diagnostic performance of dual-energy (DE) computed tomography (CT) with two simultaneously administered contrast agents (hereafter, dual contrast) with that of conventional CT in the evaluation of the presence and source of extravasation in penetrating abdominopelvic trauma.Materials and methodsInstitutional animal care and use committee approval was obtained, and the study was performed in accordance with National Institutes of Health guidelines for the care and use of laboratory animals. Five rabbits with bowel trauma, vascular penetrating trauma, or both were imaged with simultaneous iodinated intravenous and bismuth subsalicylate enteric contrast material at DE CT. Four attending radiologists and six radiology residents without prior DE CT experience each evaluated 10 extraluminal collections to identify the vascular and/or enteric origin of extravasation and assess their level of diagnostic confidence, first with virtual monochromatic images simulating conventional CT and then with DE CT material decomposition attenuation maps.ResultsOverall accuracy of identification of source of extravasation increased from 78% with conventional CT to 92% with DE CT (157 of 200 diagnoses vs 184 of 200 diagnoses, respectively; P < .001). Nine radiologists were more accurate with DE CT; one had no change. Mean confidence increased from 67% to 81% with DE CT (P < .001).ConclusionIn a rabbit abdominopelvic trauma model, dual-contrast DE CT significantly increased accuracy and confidence in the diagnosis of vascular versus enteric extravasated contrast material.

Myocardial infarction is the main contributor to heart failure. In this study we examined whether modification of a thermo-reversible cellulose-based polymer with extracellular-matrix derived functional groups could promote wound healing and improve cardiac function in a chronic rodent model of ischemic cardiomyopathy. To beneficially influence the microenvironment of the injured myocardium, we conjugated either the RGD peptide or the HepIII peptide to the polymer. In vitro cell adhesion studies showed that the peptide-modified polymer promoted cell attachment to the polymer surface. Injection of the thermo-reversible polymer into the aneurismal infarct region of the left ventricle showed that the peptide-modified polymer exhibited significantly improved left ventricular function, increased angiogenesis, decreased infarct size, and an increase in cardiomyocytes within the infarct region at 5 weeks post-treatment (P < 0.05). The results of this study demonstrate that a peptide-modified thermo-reversible polymer has the capability to alter left ventricular (LV) geometry, increase LV function, and promote myocardial regeneration in a chronic model of ischemic cardiomyopathy.

PurposeTo evaluate the feasibility of using contrast material-enhanced computed tomographic (CT) measurements of hepatic fractional extracellular space (fECS) and macromolecular contrast material (MMCM) uptake to measure severity of liver fibrosis.Materials and methodsAll procedures were approved by and executed in accordance with University of California, San Francisco, institutional animal care and use committee regulations. Twenty-one rats that received intragastric CCl(4) for 0-12 weeks were imaged with respiratory-gated micro-CT by using both a conventional contrast material and a novel iodinated MMCM. Histopathologic hepatic fibrosis was graded qualitatively by using the Ishak fibrosis score and quantitatively by using morphometry of the fibrosis area. Hepatic fECS and MMCM uptake were calculated for each examination and correlated with histopathologic findings by using uni- and multivariate linear regressions.ResultsIshak fibrosis scores ranged from a baseline of 0 in untreated animals to a maximum of 5. Histopathologic liver fibrosis area increased from 0.46% to 3.5% over the same interval. Strong correlations were seen between conventional contrast-enhanced CT measurements of fECS and both the Ishak fibrosis scores (R(2) = 0.751, P < .001) and the fibrosis area (R(2) = 0.801, P < .001). Strong negative correlations were observed between uptake of MMCM in the liver and Ishak fibrosis scores (R(2) = 0.827, P < .001), as well as between uptake of MMCM in the liver and fibrosis area (R(2) = 0.643, P = .001). Multivariate linear regression analysis showed a trend toward independence for fECS and MMCM uptake in the prediction of Ishak fibrosis scores, with an R(2) value of 0.86 (P = .081 and P = .033, respectively).ConclusionContrast-enhanced CT measurements of fECS and MMCM uptake are individually capable of being used to estimate the degree of early hepatic fibrosis in a rat model.Supplemental materialhttp://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112452/-/DC1.

PurposeTo evaluate the feasibility of using a commercially available clinical dual-energy computed tomographic (CT) scanner to differentiate the in vivo enhancement due to two simultaneously administered contrast media with complementary x-ray attenuation ratios.Materials and methodsApproval from the institutional animal care and use committee was obtained, and National Institutes of Health guidelines for the care and use of laboratory animals were observed. Dual-energy CT was performed in a set of iodine and tungsten solution phantoms and in a rabbit in which iodinated intravenous and bismuth subsalicylate oral contrast media were administered. In addition, a second rabbit was studied after intravenous administration of iodinated and tungsten cluster contrast media. Images were processed to produce virtual monochromatic images that simulated the appearance of conventional single-energy scans, as well as material decomposition images that separate the attenuation due to each contrast medium.ResultsClear separation of each of the contrast media pairs was seen in the phantom and in both in vivo animal models. Separation of bowel lumen from vascular contrast medium allowed visualization of bowel wall enhancement that was obscured by intraluminal bowel contrast medium on conventional CT scans. Separation of two vascular contrast media in different vascular phases enabled acquisition of a perfectly coregistered CT angiogram and venous phase-enhanced CT scan simultaneously in a single examination.ConclusionCommercially available clinical dual-energy CT scanners can help differentiate the enhancement of selected pairs of complementary contrast media in vivo.

Prostate-specific membrane antigen is a transmembrane glycoprotein highly expressed in many prostate cancers and can be targeted with radiolabeled antibodies for diagnosis and treatment of this disease. To serve as a radioimmunotherapeutic agent, a kinetically inert conjugate is desired to maximize tumor uptake and tumor radiation dose with minimal nonspecific exposure to bone marrow and other major organs.In this study, we assessed the pharmacokinetics and biodistribution of the 7E11 monoclonal antibody (MAb) radiolabeled with the lutetium-177 ((177)Lu)-tetraazacyclododecanetetraacetic acid conjugate system ((177)Lu-7E11) versus those of the 7E11 MAb radiolabeled with the indium-111 ((111)In)/glycyl-tyrosyl-(N,-diethylenetriaminepentaacetic acid)/lysine hydrochloride conjugate system ((111)In-7E11, also known as ProstaScint) to determine the feasibility of using (111)In-7E11 as a pre-therapeutic agent for (177)Lu-7E11 radioimmunotherapy. Pharmacokinetic and biodistribution studies of (177)Lu-7E11 in lymph node cancer of the prostate (LNCaP) xenograft mice were performed at 2, 8, 12, 24, 72, and 168 h after radiopharmaceutical administration. For (111)In-7E11, pharmacokinetic and biodistribution studies were performed at 8, 24, and 72 h. Parallel studies of (177)Lu-7E11 in non-tumor-bearing mice at 8, 24, and 72 h post-injection served as controls. Gamma scintigraphy was performed, followed by autoradiography and tissue counting, to demonstrate and quantify the distributions of radioconjugated MAb in the tumor and normal tissues.Both (177)Lu- and (111)In-7E11 conjugates demonstrated an early blood pool phase in which uptake was dominated by the blood, lung, spleen and liver, followed by uptake and retention of the radiolabeled antibody in the tumor which was most prominent at 24 h. Total accumulation of radioconjugated MAb in tumor at 24 h was greater in the case of (177)Lu-7E11 in comparison to that of (111)In-7E11. Continued accumulation in tumor was observed for the entire time course studied for both (177)Lu-7E11 and (111)In-7E11. The liver was the only major organ demonstrating a significant difference in accumulation between the two conjugates. In conclusion, pharmacokinetic and biodistribution studies of (177)Lu-7E11 in LNCaP xenograft mouse models support its potential application as a radioimmunotherapeutic agent targeting prostate cancer, and the distribution and tumor uptake of (111)In-7E11 appear to be similar to those of (177)Lu-7E11, supporting its use as a pre-therapeutic tool to assess the potential accumulation of (177)Lu-7E11 radioimmunotherapeutic at sites of prostate cancer. However, the different accumulation patterns of the (111)In and (177)Lu immunoconjugates in liver will likely prevent the use of (111)In-7E11 as a true dosimetry tool for (177)Lu-7E11 radioimmunotherapy.

We evaluated methods of imaging rat models of stroke in vivo using a single photon emission computed tomography (SPECT) system dedicated to small animal imaging (X-SPECT, Gamma Medica-Ideas, Northridge, CA). An animal model of ischemic stroke was developed for in vivo SPECT/CT imaging using the middle cerebral artery occlusion (MCAO) technique. The presence of cerebral ischemia was verified in ex vivo studies using triphenyltetrazolium chloride (TTC) staining. In vivo radionuclide imaging of cerebral blood flow was performed in rats following MCAO using dynamic planar imaging of 99mTc-exametazime with parallel hole collimation. This was followed immediately by in vivo radionuclide imaging of cerebral blood flow with 99mTc-exametazime in the same animals using 1-mm pinhole SPECT. Correlated computed tomography imaging was performed to localize radiopharmaceutical uptake. The animals were allowed to recover and ex vivo autoradiography was performed with separate administration of 99mTc-exametazime. Time activity curve of 99mTc-exametazime showed that the radiopharmaceutical uptake could be maintained for over 9 min. The activity would be expected to be relatively stable for a much longer period, although the data were only obtained for 9 min. TTC staining revealed sizable infarcts by visual observation of inexistence of TTC stain in infracted tissues of MCAO rat brains. In vivo SPECT imaging showed cerebral blood flow deficit in the MCAO model, and the in vivo imaging result was confirmed with ex vivo autoradiography. We have demonstrated a capability of imaging regions of cerebral blood flow deficit in MCAO rat brains in vivo using a pinhole SPECT dedicated to small animal imaging.

We describe in vivo single photon emission computed tomography (SPECT) and contrast-enhanced computed tomography (CT) techniques to image perfusion and vasculature structures within rodent brains using a combined SPECT-CT scanner dedicated to small animal imaging. A highly-focusing pinhole SPECT with 99mTc-exametazime (HMPAO) was acquired to image brain perfusion in rat models of stroke. We used a well-established middle cerebral artery occlusion (MCAO) model to induce stroke in rat brains. Validation of the animal model was performed by triphenyltetrazolium chloride staining and histologic analyses. The in vivo imaging results from successful MCAO models were compared against ex vivo autoradiography. A CT with a constant infusion of iodinated contrast media was acquired to image the vasculature around a rat brain including carotid arteries and the Circle of Willis. A visual comparison of image contrast to identify vascular structure in rat brains was made between contrast-enhanced and noncontrast CT images. This CT technique is useful to investigate rat models of intracranial aneurysm. We could identify the region of perfusion deficit indicating infarction through 99mTc-HMPAO SPECT. Contrast-enhanced CT revealed the vascular structure of carotid arteries and the Circle of Willis, which were invisible by noncontrast CT. We have demonstrated SPECT and contrast-enhanced CT capabilities to investigate cerebrovascular disease identification and treatment studies involving rodent models.

To establish a set of multi-PCR (MPCR) methods to detect Vibrio comma O1 serogroup (EVC) and O139 serogroup, and Vibrio parahaemolyticus rapidly and sensitively from foodstuffs.Using T139 (specific gene of O139 serogroup), ctxB and tcpA genes from V. comma, and tdh gene from V. parahaemolyticus as target sequences, we detected the anticipative amplified bands, whose sizes were relatively 417bp, 564bp, 471bp and 202bp.Excellent specificity of the amplified products could be found from both standard and wild strains of EVC, O139VC and V. parahaemolyticus. It also means that no amplified band was detected from total 35 strains of other bacilli, including salmonella, comma bacillus which do not belong to O1 and O139 serogroups. The detection limits of artificial contaminated samples such as tilapia flesh, oyster and mixture of tilapia intestines and gills were proved to be 22cfu/g in EVC, 50cfu/g in O139 and 65cfu/g in V. parahaemolyticus. Besides, it took only 8-10 hours to finish the whole process.Experiment results show that MPCR is a sensitive, convenient and time saving method suitable for detection.

The authors have developed a single photon emission computed tomography (SPECT) technique for high resolution radiotracer imaging of mice where the object is rotated instead of the scintillation camera. The system uses a 21 cm focal length pinhole collimator with a 0.5 mm diameter aperture, resulting in magnification ranging from 7 to 10 and acquisition times from 60 to 90 minutes. This method employs a plastic mouse-holding tube designed to address specific problems associated with pinhole SPECT, including low count rates and correction for shift of the center of rotation. Images of a novel "mouse heart" phantom demonstrated good image quality, uniformity, and spatial resolution. A /sup 99m/Tc-sestamibi scan of a normal mouse, electrocardiogram-gated at over 400 beats per minute, allowed assessment of regional myocardial perfusion and evaluation of ventricular wall motion. An ungated perfusion scan produced images with millimeter spatial resolution and quality comparable to human images, allowing the visualization of the left and right ventricular myocardium.

To measure the fractional distribution volume of gadopentetate dimeglumine in normal and reperfused infarcted myocardium at magnetic resonance (MR) imaging by using the fractional distribution volume of technetium 99m-diethylenetriaminepentaacetic acid (DTPA) as an independent reference.Rats were subjected to 1 hour of coronary artery occlusion and 1 hour of reperfusion before inversion-recovery echo-planar imaging or autoradiography. Regional change in relaxation rate (delta R1) ratios for myocardium over blood were compared with radioactivity ratios for myocardium over blood after the injection of 99mTc-DTPA.Both delta R1 and radioactivity ratios demonstrated equilibrium distribution and hence represent partition coefficients (lambda). The fractional distribution volumes were greater in infarcted myocardium (0.90 +/- 0.05 for gadopentetate dimeglumine and 0.89 +/- 0.04 for 99mTc-DTPA) than in normal myocardium (0.23 +/- 0.02 for gadopentetate dimeglumine and 0.16 +/- 0.01 for 99mTc-DTPA). Area at risk at autoradiography was not significantly different from that at histomorphometry. The infarction size defined by using triphenyltetrazolium chloride was 13% +/- 4 smaller than that defined by using autoradiography.The fractional distribution volumes of gadopentetate dimeglumine and 99mTc-DTPA are similar and indicate extracellular distribution in normal myocardium and intracellular as well as extracellular distribution in reperfused infarction. Because the failure of cells to exclude these agents is indicative of necrosis, contrast medium-enhanced MR imaging may be useful to quantify myocardial infarction.