Multipurpose computed tomography window for fusion display with functional imaging.

Current positron emission tomography/computed tomography (PET/CT) and single photon emission CT (SPECT)/CT displays have major drawbacks, in that the CT only shows one tissue type at a time, which leads to a suboptimal fusion display. We developed a multipurpose CT level/window aiming at enhancing fusion display. A total of thirty CT examinations as part of fluorodeoxyglucose PET/CT examinations (15 were open source from the OsiriX website and 15 from our PET facility) and the open-source software MIPAV were used. During the development phase, a nuclear medicine physician manually modified the lookup table in a way that preserved the soft tissue contrast as well as enhanced the lung and bone tissue as much as possible. The developed multipurpose CT window was used in the subsequent validation phase and scored by two nuclear medicine physicians, who scored the image quality based on a 3-point score. Descriptive statistics was used to summarize the visual scores. The multipurpose CT window is a composite of several segments of linear CT levels/windows and contains an inverted linear level/window in the low range of Hounsfield unit designed to enhance lung/soft tissue contrast. In doing so, the multipurpose CT window preserves the high soft tissue contrast; the visualization of the lung parenchyma is satisfactory; the contrast for the bone tissue is improved but remains suboptimal when compared with conventional bone window. The multipurpose CT window was found to be "very useful" (median score 3; 95% confidence interval [CI] 2.0-3.0) for the purpose of fusion with functional imaging, with a prevalence asymmetry index 0.97 (95% CI 0.83-1.0). The multipurpose CT window was developed for image fusion and is not intended for diagnostic purposes. It shows favorable similarities to conventional CT windows with only minor artifacts and allows for enhanced visualization of fused PET/CT and SPECT/CT images. The multipurpose CT window is particularly valuable for case review/demonstrations on standard personal computers and handheld devices (smartphones, tablets).

Unified model of brain tissue microstructure dynamically binds diffusion and osmosis with extracellular space geometry.

We present a universal model of brain tissue microstructure that dynamically links osmosis and diffusion with geometrical parameters of brain extracellular space (ECS). Our model robustly describes and predicts the nonlinear time dependency of tortuosity (λ=sqrt[D/D^{*}]) changes with very high precision in various media with uniform and nonuniform osmolarity distribution, as demonstrated by previously published experimental data (D = free diffusion coefficient, D^{*} = effective diffusion coefficient). To construct this model, we first developed a multiscale technique for computationally effective modeling of osmolarity in the brain tissue. Osmolarity differences across cell membranes lead to changes in the ECS dynamics. The evolution of the underlying dynamics is then captured by a level set method. Subsequently, using a homogenization technique, we derived a coarse-grained model with parameters that are explicitly related to the geometry of cells and their associated ECS. Our modeling results in very accurate analytical approximation of tortuosity based on time, space, osmolarity differences across cell membranes, and water permeability of cell membranes. Our model provides a unique platform for studying ECS dynamics not only in physiologic conditions such as sleep-wake cycles and aging but also in pathologic conditions such as stroke, seizure, and neoplasia, as well as in predictive pharmacokinetic modeling such as predicting medication biodistribution and efficacy and novel biomolecule development and testing.

Detection of Metastatic Disease in Cardiophrenic Lymph Nodes: FDG PET/CT Versus Contrast-Enhanced CT and Implications for Staging and Treatment of Disease.

OBJECTIVE: To determine whether FDG PET/CT was more sensitive than CT in detecting metastatic disease in the cardiophrenic space and whether the presence of disease in this location would change the staging and clinical management. MATERIALS AND METHODS: About 1200 PET/CT scans were retrospectively reviewed over 20 months for the presence of FDG-avid cardiophrenic lymph nodes. The SUVmax was used to quantify the metabolic activity in each of the lymph nodes. The radiographic data was used for correlation. A retrospective review of diagnostic CT reports performed within a 1-month period of time of the PET/CT in the same subset of patients determined whether cardiophrenic lymph nodes were mentioned. RESULTS: About 9 (0.8%) of the 1200 studies were found to have FDG-avid cardiophrenic lymph nodes (four males and five females with a mean age of 55 years; range 7-69, median 59). The mean SUVmax was 2.4 (range 1.2-7.9; median 1.9). Only three of the patients were found to have suspicious lymph nodes on CT. The presence of cardiophrenic lymph nodes had the potential to change the staging and/or management in three of the patients. CONCLUSION: PET/CT is more accurate in the detection of pathologic cardiophrenic lymph nodes than CT, especially when they are subcentimeter in size. When present, staging and/or management was potentially affected in 33%. Therefore, these nodes should be included in the TNM staging classification.

Calculation of renal differential function following renal transplant: retrospective validation of a simplified method.

OBJECTIVES: The estimation of differential function (DF) in post-renal transplant patients (PRTPs) is challenging because of the different distances of the native kidneys (NKs) and transplant kidney (TK) to the gamma camera and because current commercial software allows evaluation of only 2 kidneys instead of 3. We retrospectively validated a simplified method (SM) to process renal scans and hypothesized that it is comparable with the reference method (RM). PATIENTS AND METHODS: Twelve 99mTc MAG3 renal scintigraphies of 10 PRTPs were performed on a dual-head gamma camera. The RM was a 2-step process, with the left and right NKs being compared with the TK separately. The SM was a 1-step process combining both NKs together. The DF estimates were consistent with geometric means in both methods. Statistical evaluation included linear correlation and Bland-Altman analysis. RESULTS: The RM and SM showed DF of 78% ± 25% versus 79% ± 27% for the TK and 22% ± 25% versus 21% ± 27% for the NKs (P = 0.3). There was excellent correlation between SM and RM measurements (r = 0.99, P < 0.001). Bland-Altman plot demonstrated a mean difference of 1.2 ± 3.8 at a 95% confidence interval (95% CI) of agreement of -6.2 to + 8.5 for the TK and -1.2 ± 3.8 at a 95% CI of agreement of -8.5 to + 6.2 for the NKs. Only 1 (8%) of 12 scans showed a difference slightly beyond the 95% CI, indicating a good agreement between SM and RM. CONCLUSIONS: The SM offers a simple way to evaluate renal DF in PRTP and shows comparable results with the RM. It may have great potential in clinical practice; however, larger studies are needed to verify and further extend the results of this study.

Insulin resistance and breast carcinogenesis: a cross-sectional study among Iranian women with breast mass.

Despite existing epidemiologic data concerning the increased incidence of breast cancer in diabetes type 2, the association between insulin resistance and breast carcinogenesis is not yet well defined. In this cross-sectional study, we examined the homeostatic model assessment values of insulin resistance (HOMA-IR) among 82 patients with malignant breast tumor, 48 subjects with benign breast mass, and 838 healthy Iranian women. One hundred and thirty (n = 130) surgical inpatients of Tehran Central Cancer Institute (Tehran, Iran) were evaluated preoperatively. Healthy subjects were nondiabetic, nonhypertensive women aged 20-77 years from four different locations in Tehran. Age and central obesity-adjusted HOMA-IR values were 3.6 [95% confidence interval (CI), 2.8-4.4], 2.3 (1.7-2.9), and 1.7(1.6-1.8) correspondingly in subjects with malignant breast tumor, those with benign breast mass, and healthy subjects. The interaction effect of age on the association between breast mass (malignant/ benign /no breast mass) with HOMA-IR values was significant [F(54) = 10, P < 0.001, partial eta squared = 0.03]. The interaction of central obesity on this association was also significant [F(54) = 37, P < 0.001, partial eta squared = 0.11]. We conclude that the noted linkage between insulin resistance and breast cancer may indicate an underlying pathology of mammary carcinogenesis.

Assessment of an 18F-labeled phosphoramidate peptidomimetic as a new prostate-specific membrane antigen-targeted imaging agent for prostate cancer.

UNLABELLED: Prostate-specific membrane antigen (PSMA) is a transmembrane protein commonly found on the surface of late-stage and metastatic prostate cancer and a well-known imaging biomarker for staging and monitoring therapy. Although (111)In-labeled capropmab pendetide is the only approved agent available for PSMA imaging, its clinical use is limited because of its slow distribution and clearance that leads to challenging image interpretation. A small-molecule approach using radiolabeled urea-based PSMA inhibitors as imaging agents has shown promise for prostate cancer imaging. The motivation of this work is to explore phosphoramidates as a new class of potent PSMA inhibitors to develop more effective prostate cancer imaging agents with improved specificity and clearance properties. METHODS: N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB) was conjugated to S-2-((2-(S-4-amino-4-carboxybutanamido)-S-2-carboxyethoxy)hydroxyphosphorylamino)-pentanedioic acid (Phosphoramidate (1)), yielding S-2-((2-(S-4-(4-(18)F-fluorobenzamido)-4-carboxybutanamido)-S-2-carboxyethoxy)hydroxyphosphorylamino)-pentanedioic acid (3). In vivo studies were conducted in mice bearing either LNCaP (PSMA-positive) or PC-3 (PSMA-negative) tumors. PET images were acquired at 1 and 2 h with or without a preinjection of a nonradioactive version of the fluorophosphoramidate. Tissue distribution studies were performed at the end of the 2 h imaging sessions. RESULTS: Phosphoramidate (1) and its fluorobenzamido conjugate (2) were potent inhibitors of PSMA (inhibitory concentration of 50% [IC(50)], 14 and 0.68 nM, respectively). PSMA-mediated tumor accumulation was noted in the LNCaP versus the PC-3 tumor xenografts. The LNCaP tumor uptake was also blocked by the administration of nonradioactive (2) prior to imaging studies. With the exception of the kidneys, tumor-to-tissue and tumor-to-blood ratios were greater than 5:1 at 2 h. The strong kidney uptake may be due to the known PSMA expression in the mouse kidney, because significant reduction (>6-fold) in kidney activity was seen in mice injected with (2). CONCLUSION: (18)F-labeled phosphoramidate (3) is a representative of a new class of PSMA targeting peptidomimetic molecules that shows great promise as imaging agents for detecting PSMA+ prostate tumors.

Effect of laser insult on devices used to prevent stone retropulsion during ureteroscopic lithotripsy.

PURPOSE: To examine laser damage to three commercially available devices used to prevent stone retropulsion during ureteroscopic lithotripsy. MATERIALS AND METHODS: Two experiments were performed with five Accordion, Stone Cone, and NTrap devices each. All devices had a 7-mm outer diameter. The holmium:yttrium-aluminum-garnet laser was set at 8 watts. Experiment 1 was performed in an acrylic tube of 10-mm inner diameter in a saline water bath. The laser was fired against the antiretropulsion element of each device until the device could not be opened or closed. Experiment 2 was performed in a saline water bath; the laser was fired against the carrying catheter of each device until it was severed. RESULTS: For experiment 1, the mean number of laser firings against the antiretropulsion element until device failure was 2 for the NTrap, and 28.6 for the Stone Cone. The Accordion was operable after 100 laser firings. The Accordion was more laser resistant than either device (P<0.001, P<0.001), and the Stone Cone was more laser resistant than the NTrap (P<0.001). In experiment 2, mean time to break the carrying catheter was 13.6 seconds for the NTrap, 17.4 seconds for the Stone Cone, and 6.6 seconds for the Accordion. The Stone Cone and NTrap carrying catheters were more laser resistant than the Accordion (P=0.007, P=0.03 respectively), and there was no statistical difference between the Stone Cone and NTrap. CONCLUSIONS: The antiretropulsion element of the Accordion was most laser resistant, and both the Accordion and Stone Cone antiretropulsion elements were more laser resistant than the NTrap. The carrying catheters of the Stone Cone and NTrap had similar laser resistance, and both were more laser resistant than the Accordion. Urologists should be mindful of structural characteristics when using these devices.

Effect of laser insult on devices used to prevent stone retropulsion during ureteroscopic lithotripsy.

PURPOSE: To examine laser damage to three commercially available devices used to prevent stone retropulsion during ureteroscopic lithotripsy. METHODS: Two experiments were performed with 5 Accordion (Percsys, Palo Alto, CA), Stone Cone (Boston Scientific, Natick, MA), and NTrap (Cook Urological, Bloomington, IN) devices each. All devices were of 7-mm outer diameter. The holmium:YAG laser was set at 8 W. Experiment 1 was performed in an acrylic tube of 10-mm inner diameter in a saline water bath. The laser was fired against the antiretropulsion element of each device until the device could not be opened or closed. Experiment 2 was performed in a saline water bath; the laser was fired against the carrying catheter of each device until it was severed. RESULTS: For Experiment 1, the mean number of laser firings against the antiretropulsion element until device failure was 2 for the NTrap, and 28.6 for the Stone Cone. The Accordion was operable after 100 laser firings. The Accordion was more laser-resistant than either device (P < 0.001, P < 0.001, respectively), and the Stone Cone was more laser-resistant than the NTrap (P < 0.001). In Experiment 2, mean time to break the carrying catheter was 13.6 seconds for the NTrap, 17.4 seconds for the Stone Cone, and 6.6 seconds for the Accordion. The Stone Cone and NTrap carrying catheters were more laser-resistant than the Accordion (P = 0.007, P = 0.03, respectively) and there was no statistical difference between the Stone Cone and NTrap. CONCLUSIONS: The antiretropulsion element of the Accordion was most laser-resistant, and both the Accordion and Stone Cone antiretropulsion elements were more laser-resistant than the NTrap. The carrying catheters of the Stone Cone and NTrap had similar laser resistance, and both were more laser-resistant than the Accordion. Urologists should be mindful of structural characteristics when using these devices.

Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder.

OBJECTIVE: To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)-mediated neurogenic bladder in rats. MATERIALS AND METHODS: In all, 40 female Sprague-Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 microg/rat), VEGF (2 microg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (alpha-actin), Masson's trichrome and protein gene product 9.5, respectively. RESULTS: Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups. CONCLUSIONS: This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.

Association between Randall's plaque and calcifying nanoparticles.

OBJECTIVES: Randall initially described calcified subepithelial papillary plaques, which he hypothesized as nidi for urinary calculi. The discovery of calcifying nanoparticles (CNP), also referred to as nanobacteria, in calcified soft tissues has raised another hypothesis about their possible involvement in urinary stone formation. This research is the first attempt to investigate the potential association of these two hypotheses. METHODS: We collected renal papilla and blood samples from 17 human patients who had undergone laparoscopic nephrectomy. Immunohistochemical staining (IHS) was applied using monoclonal antibody (mAb) against CNP. Homogenized papillary tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) were performed on papillary samples. Serum samples were tested for CNP antigen and antibody with enzyme-linked immunosorbent assay (ELISA). RESULTS: Randall's plaques (RP) were visible on gross inspection in 11 out of 17 samples. IHS was positive for CNP antigen in 8 of the visually positive samples, but in only 1 of the remaining samples. SEM revealed spherical apatite-formations in 14 samples confirmed by EDS analysis. In cultures, all serum samples and 13 tissue homogenates grew CNP. In ELISA, 14 samples were positive for CNP-antigen and 11 samples were positive for CNP-antibody. CONCLUSION: There was evidence of a link between detection of CNP and presence of RP. Although causality was not demonstrated, these results suggest that further studies with negative control samples should be made to explore the etiology of RP formation, thus leading to a better understanding of the pathogenesis of stone formation.

Time-dependent neovasculogenesis and regeneration of different bladder wall components in the bladder acellular matrix graft in rats.

OBJECTIVES: To determine the time-dependent regeneration of different cellular components in the bladder acellular matrix graft (BAMG) and the involvement of hematopoietic stem cells in BAMG vascular regeneration. METHODS AND MATERIALS: Thirty-three male Sprague Dawley rats underwent partial cystectomy and the acellular matrices were grafted to the remaining host bladder. At 4, 7, 14, 30, 60, 90, and 180 d after grafting, animals were sacrificed and their bladders were excised and paraffin-embedded. Tissue sections were stained for determination of CD3, CD20, CD34, CD31, CD68, smooth muscle cell (SMC) alpha-actin, and neurofilament protein as well as elastin fibers and collagen typing. Cystometric evaluation of grafted bladders was also performed 3 mo after procedure. RESULTS: In acellular matrices, there was no expression of cellular markers and type-1 collagen fibers were predominant. One month after surgery, all grafted matrices were completely lined with urothelium. Polymorphonuclear cells and lymphocytes densely infiltrated BAMG during the first 2 wk after grafting; however the inflammation resolved by the first post-surgical mo. CD34+ endothelial progenitor cells (EPCs) were found in all grafts 4 d after surgery. The number of CD34+ cells increased continuously and peaked 2 mo after grafting. The increment in number of CD31+ microvessels in grafted matrices followed that of CD34+ cells and reached 144.5% of control values at third post-surgical mo. The mean number of CD34+ and CD31+ cells returned to control ranges by 6 mo after grafting. Expression of SMC alpha-actin was first visualized on day 4 and alpha-actin intensity reached to control values 6 mo after grafting. Neural elements appeared 1 wk after grafting and just 60% of normal intensity was achieved by the sixth post-surgical mo; however complete nerve bundles were found in all grafted matrices after 1 mo. Cystometric studies revealed higher bladder capacity and compliance but lower maximum intravesical pressure in grafted bladders in comparison with controls, 3 mo after surgery. CONCLUSIONS: Our results demonstrate the effective cellular regeneration in BAMG and propose a considerable role for the CD34+ EPCs in the neo-vasculogenesis of the grafts.

Polymorphisms of DNA repair genes are risk factors for prostate cancer.

DNA repair gene alterations have been shown to cause a reduction in DNA repair capacity. We hypothesised that DNA repair gene polymorphisms may be risk factors for prostate cancer (PC). To test this hypothesis, DNA samples from 165 cases of prostate cancer and healthy controls were analyzed by PCR-RFLP to determine the genotypic frequency of three DNA repair genes (XRCC1, XPC and XRCC7). We found that the frequency of 939Gln variant at XPC Lys939Gln was significantly lower in PC cases (OR=0.39, P=0.016). Haplotype analysis of XRCC1 Arg194Trp (C/T) and Arg399Gln (G/A) revealed that the frequency of the T-A haplotype was significantly higher in PC patients. This is the first report on the studies of XPC and XRCC1 Arg194Trp polymorphisms in PC, and our present data suggest that XPC Lys939Gln and the T-A haplotype of XRCC1 Arg194Trp and Arg399Gln may be risk factors for PC in Japanese.

Functional improvement in spinal cord injury-induced neurogenic bladder by bladder augmentation using bladder acellular matrix graft in the rat.

Spinal cord injury (SCI) rostral to the lumbosacral level causes bladder hyperreflexia and detrusor-sphincter dyssynergia (DSD), which are accompanied by bladder hypertrophy. We hypothesize that bladder augmentation using a bladder acellular matrix graft (BAMG) can improve the function of SCI-mediated neurogenic bladder. In female rats (n = 35), SCI was induced by transection of the spinal cord at the lower thoracic level. Eight weeks following spinalization, bladder augmentation using BAMG was performed after hemicystectomy of the hypertrophic bladder. Cystometrography was performed at 8 weeks after spinalization and again at 8 weeks after augmentation. Several urodynamic parameters were measured and the grafted bladder was histologically evaluated. Thirty one rats were alive 8 weeks after spinalization. Twenty two (71%) rats developed hyperreflexic bladders and nine (29%) rats had underactive bladders before bladder augmentation. Twenty six rats survived until 8 weeks after augmentation. Urodynamic parameters showed improvement in some bladder functions in both hyperreflexic and underactive bladders after augmentation. In addition, bladder compliance was increased in hyperreflexic bladders and decreased in underactive bladders. Bladder augmentation decreased bladder capacity in high-capacity rats and increased it in low-capacity rats. Histological evaluation showed complete regeneration of BAMG in SCI-induced neurogenic bladder at 8 weeks after augmentation. This is the first report suggesting that the voiding function in SCI-induced neurogenic bladder can be improved by augmentation using BAMG. Improved voiding function was accompanied by histological regeneration of BAMG.