Stabilizing A Vascularized Autologous Matrix with Flexible Magnesium Scaffolds to Reconstruct Dysfunctional Left Ventricular Myocardium in a Large-Animal Feasibility Study.

The surgical reconstruction of dysfunctional myocardium is necessary for patients with severe heart failure. Autologous biomaterials, such as vascularized patch materials, have a regenerative potential due to in vivo remodeling. However, additional temporary mechanical stabilization of the biomaterials is required to prevent aneurysms or rupture. Degradable magnesium scaffolds could prevent these life-threatening risks. A left ventricular transmural defect was reconstructed in minipigs with a piece of the autologous stomach. Geometrically adaptable and degradable scaffolds made of magnesium alloy LA63 were affixed on the epicardium to stabilize the stomach tissue. The degradation of the magnesium structures, their biocompatibility, physiological remodeling of the stomach, and the heart's function were examined six months after the procedure via MRI (Magnetic Resonance Imaging), angiography, µ-CT, and light microscopy. All animals survived the surgery. Stable physiological integration of the stomach patch could be detected. No ruptures of the grafts occurred. The magnesium scaffolds showed good biocompatibility. Regenerative surgical approaches for treating severe heart failure are a promising therapeutic alternative to the currently available, far from optimal options. The temporary mechanical stabilization of viable, vascularized grafts facilitates their applicability in clinical scenarios.

Cardiovascular risk in bipolar disorder - A case for the hypothalamus-pituitary-adrenal axis?

BACKGROUND: Unipolar major depressive disorder (MDD) and bipolar disorder (BD) are associated with elevated mortality risk secondary to natural causes. Cardiovascular disease (CVD) constitutes the most prevalent underlying condition. Patients with BD display higher CVD-associated excess mortality than MDD patients. Epicardial adipose tissue (EAT) volume, a known predictor of premature CV morbidity and adrenal gland (AG) volume, an indicator for chronic hypothalamus-pituitary-adrenal (HPA) axis activation, were compared in BD and MDD patients. METHODS: Magnetic resonance imaging was performed to assess EAT and AG volume in age-, gender-, and body mass index (BMI)-matched MDD (N = 27) and BD (N = 27) patients. Ten-year CV mortality risk and diabetes risk were assessed by PROCAM, ESC-SCORE, and FINDRISK, respectively; metabolic syndrome (MetS) was determined following NCEP/ATP III criteria. RESULTS: Cardiometabolic risk scores and frequency of MetS were comparable, and scores of cardiometabolic risk indices did not significantly differ in both groups. After adjustment for age, BMI, and physical activity, EAT and AG volumes were significantly higher in BD compared to MDD. Partial correlation analyses showed a significant positive association of EAT and AG volumes in BD but not in the MDD. LIMITATIONS: The modest sample size warrants confirmation in a larger cohort and the cross-sectional design does not allow for temporal or causal inferences. CONCLUSION: Our study indicates increased EAT accumulation in BD patients. This was associated with HPA axis dysregulation. Therapeutic lifestyle interventions that reduce EAT volume should be considered in clinical BD management.

Left Ventricular Wall Reconstruction with Autologous Vascularized Tunica Muscularis of Stomach in a Porcine Pilot Model.

INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. METHODS: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. RESULTS: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. CONCLUSIONS: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications.

Adipose Tissue Compartments, Inflammation, and Cardiovascular Risk in the Context of Depression.

The neurobiological and behavioral underpinnings linking mental disorders, in particular, major depressive disorder (MDD), with cardiovascular disorders are a matter of debate. Recent research focuses on visceral (intra-abdominal and epicardial) adipose tissue and inflammation and their impact on the development of cardiometabolic disorders. Intra-abdominal adipose tissue is defined as an endocrine active fat compartment surrounding inner organs and is associated with type 2 diabetes mellitus, a risk factor for the later development of cardiovascular disorders. Epicardial (pericardial) adipose tissue is a fat compartment surrounding the heart with close proximity to the arteries supporting the heart. Visceral adipose tissue (VAT) is an important source of inflammatory mediators that, in concert with other risk factors, plays a leading role in cardiovascular diseases. In conjunction with the behavioral (physical inactivity, sedentary lifestyle), psychological (adherence problems), and hormonal (dysfunction of the hypothalamus-pituitary-adrenal axis with subsequent hypercortisolism) alterations frequently accompanying MDD, an enhanced risk for cardiovascular disorders results.

Diffusion-Weighted Imaging and Mapping of T1 and T2 Relaxation Time for Evaluation of Chronic Renal Allograft Rejection in a Translational Mouse Model.

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 < 0.001) and 6 weeks after surgery (1899 ± 79 vs. 1393 ± 51 ms, p < 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 < 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.

Diffusion Weighted Imaging and T2 Mapping Detect Inflammatory Response in the Renal Tissue during Ischemia Induced Acute Kidney Injury in Different Mouse Strains and Predict Renal Outcome.

To characterize ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI) in C57BL/6 (B6) and CD1-mice by longitudinal functional MRI-measurement of edema formation (T2-mapping) and inflammation (diffusion weighted imaging (DWI)). IRI was induced with unilateral right renal pedicle clamping for 35min. 7T-MRI was performed 1 and 14 days after surgery. DWI (7 b-values) and multiecho TSE sequences (7 TE) were acquired. Parameters were quantified in relation to the contralateral kidney on day 1 (d1). Renal MCP-1 and IL-6-levels were measured by qPCR and serum-CXCL13 by ELISA. Immunohistochemistry for fibronectin and collagen-4 was performed. T2-increase on d1 was higher in the renal cortex (127 ± 5% vs. 94 ± 6%, p < 0.01) and the outer stripe of the outer medulla (141 ± 9% vs. 111 ± 9%, p < 0.05) in CD1, indicating tissue edema. Medullary diffusivity was more restricted in CD1 than B6 (d1: 73 ± 3% vs. 90 ± 2%, p < 0.01 and d14: 77 ± 5% vs. 98 ± 3%, p < 0.01). Renal MCP-1 and IL-6-expression as well as systemic CXCL13-release were pronounced in CD1 on d1 after IRI. Renal fibrosis was detected in CD1 on d14. T2-increase and ADC-reduction on d1 correlated with kidney volume loss on d14 (r = 0.7, p < 0.05; r = 0.6, p < 0.05) and could serve as predictive markers. T2-mapping and DWI evidenced higher susceptibility to ischemic AKI in CD1 compared to B6.

Application of MR diffusion imaging for non-invasive assessment of acute kidney injury after lung transplantation.

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 ±â€Š0.02 vs 2.18 ±â€Š0.05 vs 2.21 ±â€Š0.03 × 10 mm/s, P < .05). Diffusion anisotropy was reduced in all lutx recipients compared with healthy volunteers (AKI: 0.27 ±â€Š0.01 vs no AKI: 0.28 ±â€Š0.01 vs healthy: 0.33 ±â€Š0.02; P < .01). Reduction of renal ADC correlated significantly with acute loss of renal function after lutx (decrease of renal function in the postoperative period and glomerular filtration rate on the day of MRI).MR diffusion imaging enables non-invasive assessment of renal changes correlating with AKI early after lutx. Reduction of diffusion anisotropy was present in all patients after lutx, whereas marked reduction of renal ADC was observed only in the group of lutx recipients with AKI and correlated with renal function impairment.

Impact of aerobic exercise on muscle mass in patients with major depressive disorder: a randomized controlled trial.

OBJECTIVE: Sarcopenia leads to physical function impairment and at least to increasing all-cause mortality. There are notes on reduced muscle mass in patients with major depressive disorder (MDD). Whether an exercise intervention counteracts low muscle mass in patients with MDD has not been studied so far. Therefore, our study aimed at examining effects of regular aerobic exercise training on muscle mass in patients with MDD. PARTICIPANTS AND METHODS: Thirty inpatients with MDD were included in the study, of which 20 received an additional supervised exercise program. Ten patients obtained treatment as usual. Muscle mass was measured using MRI before and 6 weeks after the training period (3 times per week for 45 minutes). RESULTS: We found a significant effect of the exercise intervention on the amount of muscle mass depending on age, body mass index, and the physical activity score (P=0.042). CONCLUSION: Among other positive effects, regular exercise increases muscle mass in patients with MDD and, therefore, should be recommended as an additional treatment tool.

Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after partial hepatic ischaemia reperfusion injury: correlation with histology and serum biomarkers of liver cell injury.

OBJECTIVE: To evaluate Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after hepatic ischaemia reperfusion injury (IRI) in mice. METHODS: Partial hepatic IRI was induced in C57Bl/6 mice (n = 31) for 35, 45, 60 and 90 min. Gd-EOB-DTPA-enhanced MRI was performed 1 day after surgery using a 3D-FLASH sequence. A subgroup of n = 9 animals with 60 min IRI underwent follow-up with MRI and histology 7 days after IRI. The total liver volume was determined by manual segmentation of the entire liver. The volume of functional, contrast-enhanced liver parenchyma was quantified by a region growing algorithm (visual threshold) and an automated segmentation (Otsu's method). The percentages of functional, contrast-enhanced and damaged non-enhanced parenchyma were calculated according to these volumes. MRI data was correlated with serum liver enzyme concentrations and histologically quantified organ damage using periodic acid-Schiff (PAS) staining. RESULTS: The percentage of functional (contrasted) liver parenchyma decreased significantly with increasing ischaemia times (control, 94.4 ± 3.3%; 35 min IRI, 89.3 ± 4.1%; 45 min IRI, 87.9 ± 3.3%; 60 min IRI, 68 ± 10.5%, p < 0.001 vs. control; 90 min IRI, 55.9 ± 11.5%, p < 0.001 vs. control). The percentage of non-contrasted liver parenchyma correlated with histologically quantified liver organ damage (r = 0.637, p < 0.01) and serum liver enzyme elevations (AST r = 0.577, p < 0.01; ALT r = 0.536, p < 0.05). Follow-up MRI visualized recovery of functional liver parenchyma (71.5 ± 8.7% vs. 84 ± 2.1%, p < 0.05), consistent with less histological organ damage on day 7. CONCLUSION: We demonstrated the feasibility of Gd-EOB-DTPA-enhanced MRI for non-invasive quantification of damaged liver parenchyma following IRI in mice. This novel methodology may refine the characterization of liver disease and could have application in future studies targeting liver organ damage. KEY POINTS: • Prolonged ischaemia times in partial liver IRI increase liver organ damage. • Gd-EOB-DTPA-enhanced MRI at hepatobiliary phase identifies damaged liver volume after hepatic IRI. • Damaged liver parenchyma quantified with MRI correlates with histological liver damage. • Hepatobiliary phase Gd-EOB-DTPA-enhanced MRI enables non-invasive assessment of recovery from liver injury.

18F-FDG PET/CT for Molecular Imaging of Hepatoblastoma in Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth disorder variably characterized by macrosomia, macroglossia, congenital hypoglycemia, and hemihyperplasia. The BWS predisposes affected individuals to embryonal tumors during childhood. The BWS is caused by abnormal gene regulation in a particular region of chromosome 11. We present the case of a 1-year-old boy with BWS who underwent an F-FDG PET/CT scan for restaging of hepatoblastoma. On the F-FDG PET scan, increased tracer accumulation was observed in hepatoblastoma lesions. In addition, marked hemihyperplasia was noted. This case highlights the usefulness of F-FDG PET/CT for restaging of hepatoblastoma in BWS.

Assessment of acute kidney injury with T1 mapping MRI following solid organ transplantation.

OBJECTIVES: To evaluate T1 mapping as a non-invasive, functional MRI biomarker in patients shortly after solid organ transplantation to detect acute postsurgical kidney damage and to correlate T1 times with renal function. METHODS: 101 patients within 2 weeks after solid organ transplantation (49 kidney transplantation, 52 lung transplantation) and 14 healthy volunteers were examined by MRI between July 2012 and April 2015 using the modified Look-Locker inversion recovery (MOLLI) sequence. T1 times in renal cortex and medulla and the corticomedullary difference were compared between groups using one-way ANOVA adjusted for multiple comparison with the Tukey test, and T1 times were correlated with renal function using Pearson's correlation. RESULTS: Compared to healthy volunteers T1 times were significantly increased after solid organ transplantation in the renal cortex (healthy volunteers 987 ± 102 ms; kidney transplantation 1299 ± 101 ms, p < 0.001; lung transplantation 1058 ± 96 ms, p < 0.05) and to a lesser extent in the renal medulla. Accordingly, the corticomedullary difference was diminished shortly after solid organ transplantation. T1 changes were more pronounced following kidney compared to lung transplantation, were associated with the stage of renal impairment and significantly correlated with renal function. CONCLUSIONS: T1 mapping may be helpful for early non-invasive assessment of acute kidney injury and renal pathology following major surgery such as solid organ transplantation. KEY POINTS: • Renal cortical T1 relaxation times are prolonged after solid organ transplantation. • Cortical T1 values increase with higher stages of renal function impairment. • Corticomedullary difference decreases with higher stages of renal function impairment. • Renal cortical T1 relaxation time and corticomedullary difference correlate with renal function. • T1 mapping may be helpful for non-invasive assessment of post-operative renal pathology.

T2 Mapping for Noninvasive Assessment of Interstitial Edema in Acute Cardiac Allograft Rejection in a Mouse Model of Heterotopic Heart Transplantation.

OBJECTIVES: Heart transplantation (HTX) in mice is used to characterize gene-deficient mice and to test new treatment strategies. The purpose was to establish noninvasive magnetic resonance imaging techniques in mice to monitor pathophysiological changes of the allograft during rejection. MATERIALS AND METHODS: Magnetic resonance imaging was performed at baseline and days 1 and 6 after isogenic (n = 10, C57BL/6) and allogenic (n = 12, C57BL/6 to BALB/c) heterotopic HTX on a 7 T small animal scanner. Respiratory- and electrocardiogram-gated multislice multi-echo spin echo sequences were acquired, and parameter maps of T2 relaxation time were generated. T2 times in septal, anterior, lateral, and posterior myocardial segments as well as global T2 times were calculated and compared between groups. At day 7 animals were sacrificed and graft pathology was assessed by semiquantitative regional analysis and correlated with magnetic resonance imaging results. RESULTS: Myocardial T2 relaxation time was significantly increased in allogenic (33.4 ± 0.1 ms) and isogenic cardiac grafts (31.8 ± 1.8 ms) on day 1 after HTX compared with healthy donor hearts at baseline (23.1 ± 0.3 ms, P < 0.001). Until day 6 after HTX, myocardial T2 further increased markedly in allografts but not in isografts (43.4 ± 1.9 vs 31.2 ± 1.1 ms, P < 0.001). Mean segmental T2 values as well as mean global T2 values in allogenic compared with isogenic cardiac grafts on day 6 were significantly higher (P < 0.01). Histologically, isogenic grafts were almost normal besides small focal leukocyte infiltrates and signs of interstitial edema, most likely due to ischemia reperfusion injury (histological sum score, 0.9 ± 0.4). In allogenic HTX, histology revealed severe inflammation and tissue edema representing allograft rejection with increased histological scores (5.3 ± 0.7, P < 0.001). Higher histological scores of rejection were significantly associated with increased T2 times on a segmental and a global level. CONCLUSIONS: We could show that T2 mapping is a suitable noninvasive imaging method to monitor global and regional HTX pathologies in experimental heart transplantation in mice. Progressive prolongation of T2 time was significantly associated with pathological signs of rejection.

Evaluation of MRI/Ultrasound Fusion-Guided Prostate Biopsy Using Transrectal and Transperineal Approaches.

PURPOSE: To evaluate transrectal (TR) and transperineal (TP) approaches for MRI/ultrasound (MRI/US) fusion-guided biopsy to detect prostate cancer (PCa). MATERIALS AND METHODS: 154 men underwent multiparametric MRI and MRI/US fusion-guided biopsy between July 2012 and October 2016. 79/154 patients were biopsied with a TR approach and 75/154 with a TP approach. MRI was retrospectively analyzed according to PI-RADS version 2. PI-RADS scores were compared with histopathological results. Descriptive statistics, accuracy, and negative and positive predictive values were calculated. Histopathological results of first, second, and third MRI targeted biopsy cores were compared to evaluate the impact of one verus multiple targeted cores. RESULTS: Detection rates of PCa were 39% for TR biopsy and 75% for TP biopsy. Sensitivity/specificity for tumor detection with PI-RADS ≥ 4 were 81/69% for TR biopsy and 86/84% for TP biopsy. In 31% for TR biopsy and 19% for TP biopsy, PCa was found in the second or third MRI targeted biopsy core only. CONCLUSION: MRI/US fusion-guided biopsy may be conducted with the TR as well as the TP approach with high accuracy, giving more flexibility for diagnosis and the option for focal treatment of PCa.

68Ga-DOTA-TATE PET/CT for Molecular Imaging of Somatostatin Receptor Expression in Extra-adrenal Paraganglioma in a Case of Complete Carney Triad.

Carney triad is a very rare syndrome characterized by the synchronous or metachronous occurrence of gastrointestinal stromal tumors, pulmonary chondroma, and extra-adrenal paraganglioma. We present the case of a 36-year-old woman with complete Carney triad who underwent a Ga-DOTA-TATE PET/CT scan for restaging of metastasizing extra-adrenal paraganglioma and for evaluation of targeted radionuclide therapy potential. On the Ga-DOTA-TATE PET scan, increased tracer accumulation was observed in paraganglioma metastases. This case highlights the usefulness of Ga-DOTA-TATE PET/CT for restaging of metastasizing paraganglioma in Carney triad and the option of targeted radionuclide therapy in this entity.

Integrating MRI and Chemokine Receptor CXCR4-Targeted PET for Detection of Leukocyte Infiltration in Complicated Urinary Tract Infections After Kidney Transplantation.

Complicated urinary tract infections (UTIs) are frequent in immunosuppressed patients after kidney transplantation and may lead to allograft failure or urosepsis. Noninvasive detection of allograft involvement as well as localization of the primary site of infection are challenging. Therefore, we sought to determine whether molecularly targeted PET, combined with diffusion-weighted MRI, enables detection of leukocytes in renal allografts. Methods: Thirteen kidney transplant recipients with complicated UTIs underwent both PET with a specific CXCR4 ligand, 68Ga-pentixafor, and diffusion-weighted MRI. The spatial distribution and intensity of CXCR4 upregulation in renal allografts as determined by SUVs on PET and diffusion restriction as determined by apparent diffusion coefficients (ADCs) on MRI were analyzed and compared with urinalysis, clinical chemistry and bacteriology, and biopsy, if available. Results: Combined PET/MRI detected acute allograft infection in 9 patients and lower UTI/nonurologic infections in the remaining 4 patients. Leukocyte infiltration was identified by areas of CXCR4 upregulation compared with unaffected parenchyma in PET (SUVmean, 4.6 vs. 3.7; P < 0.01), corresponding to areas with increased cell density in MRI (ADCmin, 0.89 vs. 1.59 × 10-3 mm2/s, P < 0.01). Allograft CXCR4 signal was paralleled by CXCR4 upregulation in lymphoid organs. Histopathologic evaluation supported a correlation between CXCR4 signal and presence of leukocytes. Conclusion: Combined CXCR4-targeted PET/MRI with 68Ga-pentixafor may enable the noninvasive detection of leukocytes in renal allografts. This novel methodology may refine the characterization of infectious and inflammatory kidney diseases and may serve as a platform for future clinical studies targeting allograft infection.

Functional MRI for characterization of renal perfusion impairment and edema formation due to acute kidney injury in different mouse strains.

PURPOSE: The purpose was to characterize acute kidney injury (AKI) in C57BL/6 (B6)- and 129/Sv (Sv)-mice by noninvasive measurement of renal perfusion and tissue edema using functional MRI. METHODS: Different severities of AKI were induced in B6- and Sv-mice by renal ischemia reperfusion injury (IRI). Unilateral clamping of the renal pedicle for 35 min (moderate AKI) or 45 min (severe AKI) was done. MRI (7-Tesla) was performed 1, 7 and 28 days after surgery using a flow alternating inversion recovery (FAIR) arterial spin labeling (ASL) sequence. Maps of perfusion and T1-relaxation time were calculated. Relative MRI-parameters of the IRI kidney compared to the contralateral not-clipped kidney were compared between AKI severities and between mouse strains using unpaired t-tests. In addition, fibrosis was assessed by Masson Trichrome and collagen IV staining. RESULTS: After moderate AKI relative perfusion impairment was significantly higher in B6- than in Sv-mice at d7 (55±7% vs. 82±8%, p<0.05) and d28 (76±7% vs. 102±3%, p<0.01). T1-values increased in the early phase after AKI in both mouse strains. T1-increase was more severe after prolonged ischemia times of 45 min compared to 35 min in both mouse strains, measured in the renal cortex and outer stripe of outer medulla. Kidney volume loss (compared to the contralateral kidney) occurred already after 7 days but proceeded markedly towards 4 weeks in severe AKI. Early renal perfusion impairment was predictive for later kidney volume loss. The progression to chronic kidney disease (CKD) in the severe AKI model was similar in both mouse strains as revealed by histology. CONCLUSION: Quantification of renal perfusion and tissue edema by functional MRI allows characterization of strain differences upon AKI. Renal perfusion impairment was stronger in B6- compared to Sv-animals following moderate AKI. Prolonged ischemia times were associated with more severe perfusion impairment and edema formation in the early phase and progression to CKD within 4 weeks of observation.

Longitudinal evaluation of perfusion changes in acute and chronic renal allograft rejection using arterial spin labeling in translational mouse models.

PURPOSE: To examine the longitudinal changes of renal perfusion due to acute and chronic renal allograft rejection by using arterial spin labeling (ASL) MRI in translational mouse models of isogenic and allogenic kidney transplantation (ktx). MATERIALS AND METHODS: Acute rejection was induced by allogenic ktx of C57BL/6 (B6)-kidney grafts to BALB/c-recipients with prolonged cold ischemia (CIT) of 60 minutes (n = 13). To induce chronic rejection BALB/c-kidneys were transplanted into B6-recipients with short CIT of 30 minutes (n = 22). Isogenic grafts without rejection (n = 14 with prolonged, n = 9 with short CIT) and normal kidneys (n = 22) were used for comparison. Perfusion was measured on a 7T small-animal magnetic resonance imaging (MRI) scanner using flow-sensitive alternating inversion recovery (FAIR) ASL-sequences at day 1 and 6 (acute) or at week 3 and 6 (chronic) after surgery. Histological analyses of grafts included inflammation, vascular changes, and fibrosis. RESULTS: In the acute ktx model, ASL showed perfusion impairment in isogenic and allogenic kidney grafts. Perfusion of allografts further decreased until day 6 and remained stable in isografts without rejection (allogenic ktx 62 ± 21 vs. isogenic ktx 181 ± 39 ml/min/100g, P < 0.01). In the chronic ktx model, perfusion in isografts was similar to normal kidneys over the entire observation period. Perfusion was severely reduced in allografts compared to isografts (week 3: 28 ± 7 vs. 310 ± 46 ml/min/100g, P < 0.001, week 6: 32 ± 5 vs. 367 ± 72 ml/min/100g, P < 0.001). Histological analysis revealed severe inflammation, vascular occlusion, and rejection in allografts. Chronic rejection grafts showed endothelialitis, peritubular capillaritis, interstitial fibrosis, and tubular atrophy. CONCLUSION: ASL allows longitudinal assessment of renal perfusion impairment due to acute and chronic renal allograft rejection in translational mouse models. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1664-1672.

Reduced muscle mass in middle-aged depressed patients is associated with male gender and chronicity.

OBJECTIVE: Reduced muscle mass is a characteristic finding in sarcopenia, the central element of physical frailty syndrome, and a major cause of physical function decay, morbidity and mortality in the elderly. Studies so far demonstrated reduced muscle mass in depressed patients with an average age over 60years. An open question is whether muscle mass reduction is already observed earlier. Therefore, muscle mass was assessed in middle-aged male and female depressive patients, and the findings were related to indicators of hypothalamus-pituitary adrenal axis activation, lifestyle factors, endocrine and immune measures. METHODS: Sixty-seven depressed patients (mean age 38.6y; 58.2% female) and 26 healthy volunteers (mean age 40.5y; 61.5% female) were included. Muscle mass, adrenal gland volume, and intra-abdominal adipose tissue were assessed by magnetic resonance tomography. Laboratory parameters included fasting cortisol, pro-inflammatory cytokines, factors constituting the metabolic syndrome, and relative insulin resistance according to the homeostasis model assessment (HOMA-IR). RESULTS: We found significant effects of depression (F=4.2; P=0.043) and gender (F=182; P<0.001) on muscle mass. Muscle mass was reduced in depressed men compared to healthy men (F=3.4; P=0.044), particularly in those with chronic depression. In contrast, no such association was observed in depressed females. Adrenal gland volume and intra-abdominal fat was increased in depressed men and women, although not significantly. Correlations were observed for muscle mass with the amount of self-reported exercise and depression severity, and for depression severity with self-reported exercise. Further findings comprised lower self-reported activity and higher cortisol concentrations in depressed male and female compared to healthy probands. CONCLUSIONS: Muscle mass is reduced in middle-aged depressed men, particularly those with chronic disease course. This association is not observed in depressed females, possibly pointing to the role of female sex steroids in maintaining muscle mass. The increase of adrenal gland volume in depressed patients may point to the role of a dysregulated hypothalamus-pituitary-adrenal system. The inverse association of exercise with muscle mass demonstrates the importance of physical activity. Looking at the long term consequences of reduced muscle mass, interventions to preserve and rebuild muscle mass in depression - such as structured exercise interventions - should be recommended. SIGNIFICANT OUTCOMES: Muscle mass is decreased in male patients with major depressive disorder, particular those with chronic disease course. This difference was not observed in female depressed patients. The extent of muscle mass reduction is correlated to depression severity and inversely to physical activity, pointing to the role of depression associated inactivity. Low muscle mass is a risk factor for physical frailty, therefore interventions aiming at improving physical fitness may be recommended. LIMITATIONS: Sex steroids were not assessed in the study groups.

Multiparametric Functional MRI: Non-Invasive Imaging of Inflammation and Edema Formation after Kidney Transplantation in Mice.

BACKGROUND: Kidney transplantation (ktx) in mice is used to learn about rejection and to develop new treatment strategies. Past studies have mainly been based on histological or molecular biological methods. Imaging techniques to monitor allograft pathology have rarely been used. METHODS: Here we investigated mice after isogenic and allogenic ktx over time with functional MRI with diffusion-weighted imaging (DWI) and mapping of T2-relaxation time (T2-mapping) to assess graft inflammation and edema formation. To characterize graft pathology, we used PAS-staining, counted CD3-positive T-lymphocytes, analyzed leukocytes by means flow cytometry. RESULTS: DWI revealed progressive restriction of diffusion of water molecules in allogenic kidney grafts. This was paralleled by enhanced infiltration of the kidney by inflammatory cells. Changes in tissue diffusion were not seen following isogenic ktx. T2-times in renal cortex were increased after both isogenic and allogenic transplantation, consistent with tissue edema due to ischemic injury following prolonged cold ischemia time of 60 minutes. Lack of T2 increase in the inner stripe of the inner medulla in allogenic kidney grafts matched loss of tubular autofluorescence and may result from rejection-driven reductions in tubular water content due to tubular dysfunction and renal functional impairment. CONCLUSIONS: Functional MRI is a valuable non-invasive technique for monitoring inflammation, tissue edema and tubular function. It permits on to differentiate between acute rejection and ischemic renal injury in a mouse model of ktx.

Standardized Reporting of Prostate MRI: Comparison of the Prostate Imaging Reporting and Data System (PI-RADS) Version 1 and Version 2.

INTRODUCTION: Objective of our study was to determine the agreement between version 1 (v1) and v2 of the Prostate Imaging Reporting and Data System (PI-RADS) for evaluation of multiparametric prostate MRI (mpMRI) and to compare their diagnostic accuracy, their inter-observer agreement and practicability. MATERIAL AND METHODS: mpMRI including T2-weighted imaging, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE) of 54 consecutive patients, who subsequently underwent MRI-guided in-bore biopsy were re-analyzed according to PI-RADS v1 and v2 by two independent readers. Diagnostic accuracy for detection of prostate cancer (PCa) was assessed using ROC-curve analysis. Agreement between PI-RADS versions and observers was calculated and the time needed for scoring was determined. RESULTS: MRI-guided biopsy revealed PCa in 31 patients. Diagnostic accuracy for detection of PCa was equivalent with both PI-RADS versions for reader 1 with sensitivities and specificities of 84%/91% (AUC = 0.91 95%CI[0.8-1]) for PI-RADS v1 and 100%/74% (AUC = 0.92 95% CI[0.8-1]) for PI-RADS v2. Reader 2 achieved similar diagnostic accuracy with sensitivity and specificity of 74%/91% (AUC = 0.88 95%CI[0.8-1]) for PI-RADS v1 and 81%/91% (AUC = 0.91 95%CI[0.8-1]) for PI-RADS v2. Agreement between scores determined with different PI-RADS versions was good (reader 1: κ = 0.62, reader 2: κ = 0.64). Inter-observer agreement was moderate with PI-RADS v2 (κ = 0.56) and fair with v1 (κ = 0.39). The time required for building the PI-RADS score was significantly lower with PI-RADS v2 compared to v1 (24.7±2.3 s vs. 41.9±2.6 s, p<0.001). CONCLUSION: Agreement between PI-RADS versions was high and both versions revealed high diagnostic accuracy for detection of PCa. Due to better inter-observer agreement for malignant lesions and less time demand, the new PI-RADS version could be more practicable for clinical routine.