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For molecular imaging of atherosclerotic vessel wall activity, tracer kinetic analysis may yield improved contrast versus blood, more robust quantitative parameters, and more reliable characterization of systems biology.The authors introduce a novel dynamic whole-body positron emission tomography (PET) protocol that is enabled by rapid continuous camera table motion, followed by reconstruction of parametric data sets using voxel-based Patlak graphical analysis.Twenty-five subjects were prospectively enrolled and underwent dynamic PET up to 90 minutes after injection of 2-[Parametric MRAbsolute quantification of MR

Aim: To share our experience after 28 cryoablation treatments for prostate cancer (PCa) with histopathology, clinical data and MRI as the follow-up methods. Methods: Clinical follow-up comprised prostate-specific antigen (PSA)-measurements, PSA-density and quality of life-parameters. multi-parametric (mp)MRI pre- and post-cryoablation were retrospectively re-analyzed in 23 cases using Likert scores. Follow-up-histopathology was performed via MRI/ultrasound fusion-guided and/or systematic biopsy. Receiver operating characteristic curve analysis was performed. Results: 17 PCa (61%) were diagnosed within 12-month post-cryotherapy (infield and out-of-field disease). PSA levels and PSA density were not significantly different between patients with or without PCa recurrence. mpMRI can characterize the decrease in prostate volume and necrosis. Area under the curve for the detection of PCa was 81% (global Likert scores), 74–87% (T2), 78% (diffusion weighted imaging) and 57–78% (dynamic contrast enhanced imaging; Youden-selected cutoff ≥3). Conclusion: Besides histopathological evaluation and control biopsy, MRI might have the potential to accurately detect PCa after cryotherapy. Clinical data and interdisciplinary communication are required for efficient monitoring after cryoablation treatments for PCa.

Rationale: Tissue inflammation and subsequent fibrosis contribute to ventricle remodelling after ischemic injury and have emerged as viable therapeutic targets. Comparatively, little is understood about the dynamics of inflammation and fibrosis in nonischemic heart failure, which is challenging to interrogate longitudinally. Objective: To investigate the interplay between ventricle loading conditions, tissue inflammation, and progressive fibrosis using noninvasive multimodality molecular imaging to characterize these processes in pressure overload heart failure. Methods and Results: We evaluated cardiac inflammation using positron emission tomography radiotracer 68 Ga-pentixafor, which binds to chemokine receptor CXCR4 (CXC-motif receptor 4). Over the first 7 days after transverse aortic constriction, CXCR4 imaging identified diffuse elevated myocardial inflammation throughout the left ventricle (+34%, P P =0.003). The persistent imaging signal correlated to increased tissue fibrosis on histology. Molecular imaging at 1 week after surgery correlated independently with the change in ventricle geometry over the subsequent 3 weeks (CXCR4, r partial =0.670, P =0.024; T1, r partial =0.689, P =0.019). Alleviation of ventricle pressure by mechanical unloading restored not only cardiac function and geometry but also attenuated global inflammation and normalized T1 relaxation time. This finding demonstrates the capacity to monitor therapeutic intervention by serial molecular imaging. Conclusions: Inflammation and fibrosis are implicated in the early response to pressure overload and may be sensitively monitored by multimodality imaging. Such multimodality molecular imaging approaches may guide novel treatment strategies in nonischemic heart failure.

Objectives This study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies. Methods An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting. Results Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model. Discussion This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding.

Acute kidney injury (AKI) frequently complicates major surgery and can be associated with hypertension and progress to chronic kidney disease, but reports on blood pressure normalization in AKI are conflicting. In the present study, we investigated the effects of an angiotensin-converting enzyme inhibitor, enalapril, and a soluble epoxide hydrolase inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), on renal inflammation, fibrosis, and glomerulosclerosis in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. Male CD1 mice underwent unilateral IRI for 35 min. Blood pressure was measured by tail cuff, and mesangial matrix expansion was quantified on methenamine silver-stained sections. Renal perfusion was assessed by functional MRI in vehicle- and TPPU-treated mice. Immunohistochemistry was performed to study the severity of AKI and inflammation. Leukocyte subsets were analyzed by flow cytometry, and proinflammatory cytokines were analyzed by quantitative PCR. Plasma and tissue levels of TPPU and lipid mediators were analyzed by liquid chromatography mass spectrometry. IRI resulted in a blood pressure increase of 20 mmHg in the vehicle-treated group. TPPU and enalapril normalized blood pressure and reduced mesangial matrix expansion. However, inflammation and progressive renal fibrosis were severe in all groups. TPPU further reduced renal perfusion on days 1 and 14. In conclusion, early antihypertensive treatment worsened renal outcome after AKI by further reducing renal perfusion despite reduced glomerulosclerosis.

The structured diagnosis of chest radiographs is an important basic competence in radiology and will be required in the student teaching with the implementation of the National Competency-Based Learning Catalog Medicine (NKLM) in Germany.The aim was to evaluate the extent to which second-year students gain confidence in the diagnosis of chest radiographs through a new curricular training for the diagnosis of chest radiographs with subsequent objective structured clinical examination (OSCE) and how confident they feel about meeting the expectations of the supervising medical colleagues during the clinical clerkship.The training included four lectures and ten commented instructional films on the diagnosis of radiographs. Two years later, the students were asked how often and in what form they had contact with chest radiographs in their clinical clerkship. They were also asked how confident they felt in dealing in different areas. The students with training were also asked to what extent the lectures and the instructional films were helpful. The results of students in the last year without and the first year with training and OSCE were compared using the Mann-Whitney U test for independent samples.The frequency of dealing with chest radiographs was comparably high among students with and without training. The students with training and OSCE felt more confident and better prepared in dealing with chest radiographs than the students without training (varying between p 0.001 and p = 0.148). They rated the educational films as more helpful than the lectures (mean 2.85 ± 0.76 vs. 3.41 ± 0.68 on a four-point scale).With early training, students' confidence in dealing with chest radiographs can be sustainably increased.

To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases between 68 Ga-PSMA ligand PET/CT and conventional imaging in a comparative retrospective contouring study. Twenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwent 68 Ga-PSMA ligand PET/CT in addition to conventional imaging techniques such as CT and/or MR imaging for restaging. All patients were diagnosed with at least one lymph node metastasis. TVs were manually delineated in two different ways: (a) based on conventional imaging (CT/MRI) and (b) based on conventional imaging (CT/MRI) plus 68 Ga-PSMA ligand PET/CT. The size of TVs, overlap rates, and subjective assessment of the difficulty of TV delineation reported by the radiation oncologist (easy/moderate/difficult) were compared. With the additional information from PSMA ligand PET, 47 lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9–565.2] versus 44.9 ml [range 4.9–481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TVPET/TVCT/MRI × 100) were 45.7% (range 0–96.9) for the GTV and 71.7% (range 9.8–98.2) for the CTV. The assessment of difficulty of contouring revealed that contouring with the additional imaging information of the PET was categorized as easy/moderate in 92% (23/25) and as difficult in 8% (2/25) of the cases, whereas contouring based on CT/MRI without PET was categorized as difficult in 56% (14/25) and as easy/moderate in 44% of the cases (11/25; p = 0.003). 68 Ga-PSMA ligand PET/CT is superior to conventional cross-sectional imaging for the delineation of lymph node metastases from prostate cancer. PET-based TV delineation allows for smaller target volumes and should be considered the standard for irradiation of metachronous lymph node metastases in recurrent prostate cancer. Conventional imaging is not sufficiently sensitive for radio-oncological treatment concepts in oligometastatic prostate cancer.

Purpose To determine the patterns of progression after 68Ga prostate-specific membrane antigen (PSMA)-ligand positron emission tomography (PET)/computed tomography (CT)-guided radiation therapy (RT) for recurrent oligometastatic prostate cancer (PCa). Methods and Materials One hundred and eight patients with increased prostate-specific antigen levels, who received 68Ga-PSMA-ligand PET/CT-guided RT for recurrent oligometastatic disease after primary therapy for PCa were included. The biochemical progression-free survival and distant disease-free survival after PSMA-ligand PET/CT-guided RT were determined. The patterns of progression were determined using renewed 68Ga-PSMA-ligand PET/CT in patients with biochemical progression and compared with the clinical target volume of the 68Ga-PSMA-ligand PET/CT-guided RT. The frequency of infield and outfield relapses was recorded. Results A total of 97.2% (105 of 108) of patients showed a decrease in prostate-specific antigen levels after RT and were classified as biochemical responders. After the median follow-up of 18 months, 43.5% (47 of 108) of the patients experienced biochemical progression, resulting in an estimated biochemical progression-free survival of 16 months. Renewed 68Ga-PSMA-ligand PET/CT allowed localization of recurrent disease in 91.7% (33 of 36) of patients. Analysis of the patterns of progression resulted in a cumulative infield relapse rate of 12.1% (4 of 33) and a cumulative outfield relapse rate of 87.9% (29 of 33). The resultant median disease-free survival was 11 months. In terms of the pattern of progression, we observed a shift in the pattern of metastases toward skeletal involvement and distant lymph node metastases. Of these patients, 45.5% (15 of 33) were treated with further RT to delay initiation or escalation of systemic therapies. Conclusion PSMA-ligand PET/CT-guided RT for relapsed PCa with limited tumor burden allowed individualization of treatment approaches, provided effective local control, and resulted in considerably prolonged biochemical progression-free survival. As indicated by the PSMA-ligand PET/CT-based patterns of progression, repeated PET/CT-guided RT may represent a treatment option in well-selected patients with relapse after RT for oligometastatic disease.

Supplemental Digital Content is available in the text., Background. Systemic exposure to high-dose corticosteroids effectively combats acute rejection after kidney transplantation, but at the cost of substantial side effects. In this study, a murine acute renal allograft rejection model was used to investigate whether liposomal-encapsulated prednisolone (LP) facilitates local exposure to enhance its therapeutic effect. Methods. Male BalbC recipients received renal allografts from male C57BL/6J donors. Recipients were injected daily with 5 mg/kg cyclosporine A and received either 10 mg/kg prednisolone (P), or LP intravenously on day 0, 3, and 6, or no additional treatment. Functional magnetic resonance imaging (fMRI) was performed on day 6 to study allograft perfusion and organs were retrieved on day 7 for further analysis. Results. Staining of polyethylene-glycol-labeled liposomes and high performance liquid chromatography analysis revealed accumulation in the LP treated allograft. LP treatment induced the expression of glucocorticoid responsive gene Fkbp5 in the allograft. Flow-cytometry of allografts revealed liposome presence in CD45+ cells, and reduced numbers of F4/80+ macrophages, and CD3+ T-lymphocytes upon LP treatment. Banff scoring showed reduced interstitial inflammation and tubulitis and fMRI analysis revealed improved allograft perfusion in LP versus NA mice. Conclusions. Liposomal delivery of prednisolone improved renal bio-availability, increased perfusion and reduced cellular infiltrate in the allograft, when compared with conventional prednisolone. Clinical studies should reveal if treatment with LP results in improved efficacy and reduced side effects in patients with renal allograft rejection.

We hypothesized that multiparametric MRI is able to non-invasively assess, characterize and monitor renal allograft pathology in a translational mouse model of chronic allograft rejection. Chronic rejection was induced by allogenic kidney transplantation (ktx) of BALB/c-kidneys into C57BL/6-mice (n = 23). Animals after isogenic ktx (n = 18) and non-transplanted healthy animals (n = 22) served as controls. MRI sequences (7T) were acquired 3 and 6 weeks after ktx and quantitative T1, T2 and apparent diffusion coefficient (ADC) maps were calculated. In addition, in a subset of animals, histological changes after ktx were evaluated. Chronic rejection was associated with a significant prolongation of T1 time compared to isogenic ktx 3 (1965 ± 53 vs. 1457 ± 52 ms, p &lt, 0.001) and 6 weeks after surgery (1899 ± 79 vs. 1393 ± 51 ms, p &lt, 0.001). While mean T2 times and ADC were not significantly different between allogenic and isogenic kidney grafts, histogram-based analysis of ADC revealed significantly increased tissue heterogeneity in allografts at both time points (standard derivation/entropy/interquartile range, p &lt, 0.05). Correspondingly, histological analysis showed severe inflammation, graft fibrosis and tissue heterogeneity in allogenic but not in isogenic kidney grafts. In conclusion, renal diffusion weighted imaging and mapping of T2 and T1 relaxation times enable detection of chronic renal allograft rejection in mice. The combined quantitative assessment of mean values and histograms provides non-invasive information of chronic changes in renal grafts and allows longitudinal monitoring.

The article Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI

Background: Ischemia reperfusion injury (IRI) plays a major role in solid organ transplantation. The length of warm ischemia time is critical for the extent of tissue damage in renal IRI. In this experimental study we hypothesized that local release of labile heme in renal tissue is triggered by the duration of warm ischemia (15 vs. 45 min IRI) and mediates complement activation, cytokine release, and inflammation. Methods: To induce IRI, renal pedicle clamping was performed in male C57BL/6 mice for short (15 min) or prolonged (45 min) time periods. Two and 24 h after experimental ischemia tissue injury labile heme levels in the kidney were determined with an apo-horseradish peroxidase assay. Moreover, renal injury, cytokines, and C5a and C3a receptor (C5aR, C3aR) expression were determined by histology, immunohistochemistry and qPCR, respectively. In addition, in vitro studies stimulating bone marrow-derived macrophages with LPS and the combination of LPS and heme were performed and cytokine expression was measured. Results: Inflammation and local tissue injury correlated with the duration of warm ischemia time. Labile heme concentrations in renal tissue were significantly higher after prolonged (45 min) as compared to short (15 min) IRI. Notably, expression of the inducible heme-degrading enzyme heme oxygenase-1 (HO-1) was up-regulated in kidneys after prolonged, but not after short IRI. C5aR, the pro-inflammatory cytokines IL-6 and TNF-alpha as well as pERK were up-regulated after prolonged, but not after short ischemia times. Consecutively, neutrophil infiltration and up-regulation of pro-fibrotic cytokines such as CTGF and PAI were more pronounced in prolonged IRI in comparison to short IRI. In vitro stimulation of macrophages with LPS revealed that IL-6 expression was enhanced in the presence of heme. Finally, administration of the heme scavenger human serum albumin (HSA) reduced the expression of pro-inflammatory cytokines, C3a receptor and improved tubular function indicated by enhanced alpha 1 microglobulin (A1M) absorption after IRI. Conclusions: Our data show that prolonged duration of warm ischemia time increased labile heme levels in the kidney, which correlates with IRI-dependent inflammation and up-regulation of anaphylatoxin receptor expression.

Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although (18)F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with (18)F-FDG can be serially imaged in the early stages of pressure-overload–induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. (18)F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 ± 10.2 μL vs. 23.8 ± 1.7 μL, P < 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9% ± 9.7% vs. 59.2% ± 4.4%, P < 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = −0.669, P = 0.010). PET imaging identified significantly higher left ventricular (18)F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 ± 4.1 percentage injected dose [%ID]/g vs. 3.8 ± 0.9 %ID/g, P < 0.001) and on day 7 (7.8 ± 3.7 %ID/g vs. 3.0 ± 0.8 %ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The (18)F-FDG signal correlated with ejection fraction (r = −0.75, P = 0.01) and ventricular volume (r = 0.75, P < 0.01). Western immunoblotting demonstrated a 60% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using (18)F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload.

The presence of B-cell clusters in allogenic T cell-mediated rejection (TCMR) of kidney allografts is linked to more severe disease entities. In this study we characterized B-cell infiltrates in patients with TCMR and examined the role of serum CXCL-13 in these patients and experimentally. CXCL-13 serum levels were analyzed in 73 kidney allograft recipients at the time of allograft biopsy. In addition, four patients were evaluated for CXCL13 levels during the first week after transplantation. ELISA was done to measure CXCL-13 serum levels. For further mechanistic understanding, a translational allogenic kidney transplant (ktx) mouse model for TCMR was studied in BalbC recipients of fully mismatched transplants with C57BL/6 donor kidneys. CXCL-13 serum levels were measured longitudinally, CD20 and CD3 composition and CXCL13 mRNA in tissue were examined by flow cytometry and kidneys were examined by histology and immunohistochemistry. We found significantly higher serum levels of the B-cell chemoattractant CXCL13 in patients with TCMR compared to controls and patients with borderline TCMR. Moreover, in patients with acute rejection within the first week after ktx, a &gt, 5-fold CXCL13 increase was measured and correlated with B-cell infiltrates in the biopsies. In line with the clinical findings, TCMR in mice correlated with increased systemic serum-CXCL13 levels. Moreover, renal allografts had significantly higher CXCL13 mRNA expression than isogenic controls and showed interstitial CD20+ B-cell clusters and CD3+ cell infiltrates accumulating in the vicinity of renal vessels. CXCL13 blood levels correlate with B-cell involvement in TCMR and might help to identify patients at risk of a more severe clinical course of rejection.

Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of Ostn, which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic peptide signaling. By generating skeletal muscle specific Ostn knock-out and overexpressing mice, we demonstrate that reduced skeletal muscle Musclin levels exaggerate, while its overexpression in muscle attenuates cardiac dysfunction and myocardial fibrosis during pressure overload. Mechanistically, Musclin enhances the abundance of C-type natriuretic peptide (CNP), thereby promoting cardiomyocyte contractility through protein kinase A and inhibiting fibroblast activation through protein kinase G signaling. Because we also find reduced OSTN expression in skeletal muscle of heart failure patients, augmentation of Musclin might serve as therapeutic strategy., Cachexia is associated with poor prognosis in heart failure. Here the authors show that mice and patients with cardiac cachexia display reduced skeletal muscle expression and circulating levels of Musclin. Musclin ablation in skeletal muscle worsens, while its muscle-specific overexpression ameliorates heart failure in mice.

To assess whether MR diffusion imaging may be applied for non-invasive detection of renal changes correlating with clinical diagnosis of acute kidney injury (AKI) in patients after lung transplantation (lutx). Fifty-four patients (mean age 49.6, range 26–64 years) after lutx were enrolled in a prospective clinical study and underwent functional MR imaging of the kidneys in the early postoperative period. Baseline s-creatinine ranged from 39 to 112 μmol/L. For comparison, 14 healthy volunteers (mean age 42.1, range 24–59 years) underwent magnetic resonance imaging (MRI) using the same protocol. Renal tissue injury was evaluated using quantification of diffusion and diffusion anisotropy with diffusion-weighted (DWI) and diffusion-tensor imaging (DTI). Renal function was monitored and AKI was defined according to Acute-Kidney-Injury-Network criteria. Statistical analysis comprised one-way ANOVA and Pearson correlation. 67% of lutx patients (36/54) developed AKI, 47% (17/36) had AKI stage 1, 42% (15/36) AKI stage 2, and 8% (3/36) severe AKI stage 3. Renal apparent diffusion coefficients (ADCs) were reduced in patients with AKI, but preserved in transplant patients without AKI and healthy volunteers (2.07 ± 0.02 vs 2.18 ± 0.05 vs 2.21 ± 0.03 × 10–3 mm2/s, P

To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases betweenTwenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwentWith the additional information from PSMA ligand PET, 47 lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9-565.2] versus 44.9 ml [range 4.9-481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TV

To determine the patterns of progression afterOne hundred and eight patients with increased prostate-specific antigen levels, who receivedA total of 97.2% (105 of 108) of patients showed a decrease in prostate-specific antigen levels after RT and were classified as biochemical responders. After the median follow-up of 18 months, 43.5% (47 of 108) of the patients experienced biochemical progression, resulting in an estimated biochemical progression-free survival of 16 months. RenewedPSMA-ligand PET/CT-guided RT for relapsed PCa with limited tumor burden allowed individualization of treatment approaches, provided effective local control, and resulted in considerably prolonged biochemical progression-free survival. As indicated by the PSMA-ligand PET/CT-based patterns of progression, repeated PET/CT-guided RT may represent a treatment option in well-selected patients with relapse after RT for oligometastatic disease.

Severe ischemia reperfusion injury (IRI) results in rapid complement activation, acute kidney injury and progressive renal fibrosis. Little is known about the roles of the C5aR1 and C5aR2 complement receptors in IRI. In this study C5aR1–/– and C5aR2–/– mice were compared to the wild type in a renal IRI model leading to renal fibrosis. C5a receptor expression, kidney morphology, inflammation, and fibrosis were measured in different mouse strains one, seven and 21 days after IRI. Renal perfusion was evaluated by functional magnetic resonance imaging. Protein abundance and phosphorylation were assessed with high content antibody microarrays and Western blotting. C5aR1 and C5aR2 were increased in damaged tubuli and even more in infiltrating leukocytes after IRI in kidneys of wild-type mice. C5aR1–/– and C5aR2–/– animals developed less IRI-induced inflammation and showed better renal perfusion than wild-type mice following IRI. C5aR2–/– mice, in particular, had enhanced tubular and capillary regeneration with less renal fibrosis. Anti-inflammatory IL-10 and the survival/growth kinase AKT levels were especially high in kidneys of C5aR2–/– mice following IRI. LPS caused bone marrow–derived macrophages from C5aR2–/– mice to release IL-10 and to express the stress response enzyme heme oxygenase-1. Thus, C5aR1 and C5aR2 have overlapping actions in which the kidneys of C5aR2–/– mice regenerate better than those in C5aR1–/– mice following IRI. This is mediated, at least in part, by differential production of IL-10, heme oxygenase-1 and AKT.

Objectives Standardization is an important milestone in the validation of DWI-based parameters as imaging biomarkers for renal disease. Here, we propose technical recommendations on three variants of renal DWI, monoexponential DWI, IVIM and DTI, as well as associated MRI biomarkers (ADC, D, D*, f, FA and MD) to aid ongoing international efforts on methodological harmonization. Materials and methods Reported DWI biomarkers from 194 prior renal DWI studies were extracted and Pearson correlations between diffusion biomarkers and protocol parameters were computed. Based on the literature review, surveys were designed for the consensus building. Survey data were collected via Delphi consensus process on renal DWI preparation, acquisition, analysis, and reporting. Consensus was defined as ≥ 75% agreement. Results Correlations were observed between reported diffusion biomarkers and protocol parameters. Out of 87 survey questions, 57 achieved consensus resolution, while many of the remaining questions were resolved by preference (65–74% agreement). Summary of the literature and survey data as well as recommendations for the preparation, acquisition, processing and reporting of renal DWI were provided. Discussion The consensus-based technical recommendations for renal DWI aim to facilitate inter-site harmonization and increase clinical impact of the technique on a larger scale by setting a framework for acquisition protocols for future renal DWI studies. We anticipate an iterative process with continuous updating of the recommendations according to progress in the field.

Supplemental Digital Content is available in the text, To evaluate readout-segmented echoplanar (rsEPI) diffusion weighted imaging (DWI) for multiparametric (mp) magnetic resonance imaging (MRI) of the prostate compared to the established single-shot echoplanar imaging (ssEPI) sequence. One hundred ten consecutive patients with clinical suspicion of prostate cancer underwent mp prostate MRI using both, the ssEPI and the rsEPI DWI sequence. For an objective assessment, delineation of the prostate shape on both DWI sequences was compared to T2-weighted images by measuring organ diameters. Apparent diffusion coefficient (ADC) values, image contrast and contrast-to-noise ratio (CNR) were compared between the 2 sequences on a region-of-interest-based analysis. Diagnostic accuracy for quantitative ADC-values was calculated. Histopathology from MRI/ultrasound fusion-guided biopsy was used as reference standard. For a subjective assessment, 2 independent readers visually assessed image quality of both sequences using Likert-scales. Delineation of the prostate shape was more accurate with rsEPI compared to ssEPI. ADC values in target lesions were not significantly different but significantly higher in the surrounding normal prostatic tissue of the transition zone. CNR was comparable between ssEPI and rsEPI. Sensitivity and specificity were good for both sequences with 84/84% and 82/73% with a Youden selected cut-off of ADC = 0.971∗10−3 mm2/s for rsEPI and 1.017∗10−3 mm2/s for ssEPI. Anatomic artifacts were significantly less and SNR was lower on rsEPI compared to ssEPI in the subjective analysis. Delineation of the prostate shape was more accurate with rsEPI DWI than with ssEPI DWI with less anatomic artifacts and higher subjective SNR and image quality on rsEPI DW images. Diagnostic ability of quantitative ADC-values was not significantly different between the 2 sequences. Thus, rsEPI DWI might be more suitable for prostate MRI with regard to MRI-guided targeted biopsy and therapy planning.