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To characterise the corticoreticular pathway (CRP) in a case–control cohort of adolescent idiopathic scoliosis (AIS) patients using high-resolution slice-accelerated readout-segmented echo-planar diffusion tensor imaging (DTI) to enhance the discrimination of small brainstem nuclei in comparison to automated whole-brain volumetry and tractography and their clinical correlates. Thirty-four participants (16 AIS patients, 18 healthy controls) underwent clinical and orthopaedic assessments and brain magnetic resonance imaging (MRI) on a 3 T MRI machine. Automated whole-brain volume-based morphometry, tract-based spatial statistics analysis, and manual CRP tractography by two independent raters were performed. Intra-rater and inter-rater agreement of DTI metrics from CRP tractography were assessed by intraclass correlation coefficient. Normalised structural brain volumes and DTI metrics were compared between groups using Student's t -tests. Linear correlation analysis between imaging parameters and clinical scores was also performed. AIS patients demonstrated a significantly larger pons volume compared to controls (p= 0.006). Significant inter-side CRP differences in mean (p= 0.02) and axial diffusivity (p= 0.01) were found in patients only. Asymmetry in CRP fractional anisotropy significantly correlated with the Cobb angle (p= 0.03). Relative pontine hypertrophy and asymmetry in CRP DTI metrics suggest central supranuclear inter-hemispheric imbalance in AIS, and support the role of the CRP in axial muscle tone. Longitudinal evaluation of CRP DTI metrics in the prediction of AIS progression may be clinically relevant. • The corticoreticular pathway (CRP) controls truncal muscle tone and posture. • RESOLVE DTI enhances discrimination of small brainstem nuclei for CRP tractography. • AIS patients demonstrated a significantly larger pons volume compared to controls. • Inter-side differences in CRP mean and axial diffusivity are only found in patients. • CRP fractional anisotropy correlated with the Cobb angle in AIS patients. [ABSTRACT FROM AUTHOR]

Introduction To assess if parameters in intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) can be used to evaluate early renal fibrosis in a mouse model of diabetic nephropathy. Materials & methods In a population of 38 male CD1 mice (8 weeks old, 20–30 g), streptozotocin induced diabetes was created in 20 mice via a single intraperitoneal injection of streptozotocin at 150 mg/kg, while 18 mice served as control group. IVIM parameters were acquired at 0, 12 and 24 weeks after injection of streptozotocin using a range of b values from 0 to 1200 s/mm 2 . DTI parameters were obtained using 12 diffusion directions and lower b values of 0, 100 and 400 s/mm 2 . DTI and IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of the right kidney was performed in all mice. Results were analyzed using an unpaired t -test with P < 0.05 considered statistically significant. Results Renal cortex fractional anisotropy (FA) was significantly lower in the diabetes group at week 12 as compared with the control group. Renal cortex apparent diffusion coefficient and tissue diffusivity were significantly higher in the diabetes group at week 12 compared with the control group at 12 weeks. Blood flow was significantly decreased at the renal medulla at 24 weeks. Histopathological analysis confirmed fibrosis in the diabetes group at 24 weeks. Conclusion FA is significantly reduced in diabetic nephropathy. FA might serve a potential role in the detection and therapy monitoring of early diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Dynamic contrast-enhanced (DCE) CT imaging of four patients with hepatocellular carcinoma (HCC) was performed using a dual-phase imaging protocol designed with initial rapid dynamic imaging to capture the initial increase in contrast medium enhancement in order to assess perfusion, followed by a delayed imaging phase with progressively longer intervals to monitor subsequent tissue enhancement behaviour in order to assess tissue permeability. The DCE CT images were analysed using a dual-input two-compartment distributed parameter model to yield separate estimates for blood flow and permeability, as well as fractional intravascular and extravascular volumes. The HCCs and surrounding cirrhotic liver tissues were found to exhibit enhancement curves that can be appropriately described by two distinct compartments separated by a semipermeable barrier. Early contrast arrival was also found for HCC as compared with background liver. These findings are consistent with the current understanding of sinusoidal capillarization and hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Background and purpose: This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson's disease (PD) and explored their associations with cardiovascular risk factors and cognitive performance. Methods: A total of 175 non‐demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD‐MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10‐year cardiovascular risk score (mFRS). Results: A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD‐MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P = 0.015) and periventricular WMH (P = 0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD‐MCI (P = 0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD‐MCI compared with patients in the 1st quintile of periventricular WMH burden (P = 0.004). However, total brain WMH burden was not associated with PD‐MCI (P = 0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors. Conclusion: Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Preclinical studies have demonstrated the additive effect of rapamycin with bevacizumab for hepatocellular carcinoma treatment. We conducted a Phase 1 study to evaluate the safety and pharmacokinetics of the combination in patients with hepatocellular carcinoma. Methods: Adult participants with advanced hepatocellular carcinoma received intravenous bevacizumab (5mg/kg every 14days) and oral rapamycin (1–6mg/day; 3+3 dose escalation design). Computed tomography assessed tumour response and treatment safety. Pharmacokinetics assessment established rapamycin blood concentrations pre- and post-dose. Dynamic contrast-enhanced computed tomography analysed the tumour region for blood flow, permeability surface area product, fractional intravascular blood volume and extracellular–extravascular volume. Results: Twenty-four participants were treated. There were two dose limiting toxicities with rapamycin 5mg: grade 3 thrombocytopenia and grade 3 mucositis. The maximally tolerated dose of rapamycin was 4mg. Adverse events (grade 1–2) included hyperglycaemia (83%), thrombocytopenia (75%), fatigue (46%), mucositis (46%), anorexia (42%), diarrhoea (33%) and proteinuria (12.5%). Of 20 evaluable participants, one reached complete response that lasted 4.5months, two reached partial response, 14 reached stable disease and three had progressive disease. Median overall survival was 9.4months; progression-free survival was 5.5months. Dose level and steady state area under the concentration time curve for hour zero to infinity of rapamycin correlated inversely with blood flow rate and change in permeability-surface area. After 22days of treatment, there were significant reductions from baseline in blood flow rate, permeability-surface area and fractional intracellular blood volume. Conclusions: The recommended Phase 2 dose of rapamycin is 4mg in combination with bevacizumab. Evidence of anti-vascular activity was observed together with promising clinical activity. [Copyright &y& Elsevier]