Reproducibility and Repeatability of Intravoxel Incoherent Motion MRI Acquisition Methods in Liver.

BACKGROUND: Intravoxel incoherent motion (IVIM) diffusion weighted MRI (DWI) has potential for evaluating hepatic fibrosis but image acquisition technique influence on diffusion parameter estimation bears investigation. PURPOSE: To minimize variability and maximize repeatably in abdominal DWI in terms of IVIM parameter estimates. STUDY TYPE: Prospective test-retest and image quality comparison. SUBJECTS: Healthy volunteers (3F/7M, 29.9 ± 12.9 years) and Family Study subjects (18F/12M, 51.7 ± 16.7 years), without and with liver steatosis. FIELD STRENGTH/SEQUENCE: Abdominal single-shot echo-planar imaging (EPI) and simultaneous multi-slice (SMS) DWI sequences with respiratory triggering (RT), breath-holding (BH), and navigator echo (NE) at 3 Tesla. ASSESSMENT: SMS-BH, EPI-NE, and SMS-RT data from twice-scanned healthy volunteers were analyzed using 6 × b-values (0-800 s⋅mm-2 ) and lower (LO) and higher (HI) b-value ranges. Family Study subjects were scanned using SMS and standard EPI sequences. The biexponential IVIM model was used to estimate fast-diffusion coefficient (Df ), fraction of fast diffusion (f), and slow-diffusion coefficient (Ds ). Scan time, estimated signal-to-noise ratio (eSNR), eSNR per acquisition, and distortion ratio were compared. STATISTICAL TESTS: Coefficients of variation (CoV) and Bland Altman analyses were performed for test-retest repeatability. Interclass correlation coefficient (ICC) assessed interobserver agreement with P < 0.05 deemed significant. RESULTS: Within-subject CoVs among volunteers (N = 10) for f and Ds were lowest in EPI-NE-LO (11.6%) and SMS-RT-HI (11.1%). Inter-observer ICCs for f and Ds were highest for EPI-NE-LO (0.63) and SMS-RT-LO (0.76). Df could not be estimated for most subjects. Estimated eSNR (EPI = 21.9, SMS = 4.7) and eSNR time (EPI = 6.7, SMS = 16.6) were greater for SMS, with less distortion in the liver region (DR-PE: EPI = 23.6, SMS = 13.1). DATA CONCLUSION: Simultaneous multislice acquisitions had significantly less variability and higher ICCs of Ds , higher eSNR, less distortion, and reduced scan time compared to EPI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Pioglitazone reduces epicardial fat and improves diastolic function in patients with type 2 diabetes.

AIMS: To examine the effect of pioglitazone on epicardial (EAT) and paracardial adipose tissue (PAT) and measures of diastolic function and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). METHODS: Twelve patients with T2DM without clinically manifest cardiovascular disease and 12 subjects with normal glucose tolerance (NGT) underwent cardiac magnetic resonance imaging to quantitate EAT and PAT and diastolic function before and after pioglitazone treatment for 24 weeks. Whole-body insulin sensitivity was measured with a euglycaemic insulin clamp and the Matsuda Index (oral glucose tolerance test). RESULTS: Pioglitazone reduced glycated haemoglobin by 0.9% (P < 0.05), increased HDL cholesterol by 7% (P < 0.05), reduced triacylglycerol by 42% (P < 0.01) and increased whole-body insulin-stimulated glucose uptake by 71% (P < 0.01) and Matsuda Index by 100% (P < 0.01). In patients with T2DM, EAT (P < 0.01) and PAT (P < 0.01) areas were greater compared with subjects with NGT, and decreased by 9% (P = 0.03) and 9% (P = 0.09), respectively, after pioglitazone treatment. Transmitral E/A flow rate and peak left ventricular flow rate (PLVFR) were reduced in T2DM versus NGT (P < 0.01) and increased following pioglitazone treatment (P < 0.01-0.05). At baseline normalized PLVFR inversely correlated with EAT (r = -0.45, P = 0.03) but not PAT (r = -0.29, P = 0.16). E/A was significantly and inversely correlated with EAT (r = -0.55, P = 0.006) and PAT (r = -0.40, P = 0.05). EAT and PAT were inversely correlated with whole-body insulin-stimulated glucose uptake (r = -0.68, P < 0.001) and with Matsuda Index (r = 0.99, P < 0.002). CONCLUSION: Pioglitazone reduced EAT and PAT areas and improved left ventricular (LV) diastolic function in T2DM. EAT and PAT are inversely correlated (PAT less strongly) with LV diastolic function and both EAT and PAT are inversely correlated with measures of insulin sensitivity.

Combination therapy with pioglitazone/exenatide/metformin reduces the prevalence of hepatic fibrosis and steatosis: The efficacy and durability of initial combination therapy for type 2 diabetes (EDICT).

AIM: To compare the efficacy of triple therapy (metformin/exenatide/pioglitazone) versus stepwise conventional therapy (metformin → glipizide → glargine insulin) on liver fat content and hepatic fibrosis in newly diagnosed, drug-naïve patients with type 2 diabetes. METHODS: Sixty-eight patients completed the 6-year follow-up and had an end-of-study (EOS) FibroScan to provide measures of steatosis (controlled attenuation parameter [CAP] in dB/m) and fibrosis (liver stiffness measurement [LSM] in kPa); 59 had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to measure liver fat. RESULTS: At EOS, HbA1c was 6.8% and 6.0% in triple and conventional therapy groups, respectively (P = .0006). Twenty-seven of 39 subjects (69%) receiving conventional therapy had grade 2/3 steatosis (CAP, FibroScan) versus nine of 29 (31%) in triple therapy (P = .0003). Ten of 39 (26%) subjects receiving conventional therapy had stage 3/4 fibrosis (LSM) versus two of 29 (7%) in triple therapy (P = .04). Conventional therapy subjects had more liver fat (MRI-PDFF) than triple therapy (12.9% vs. 8.8%, P = .03). The severity of steatosis (CAP) (r = 0.42, P < .001) and fibrosis (LSM) (r = -0.48, P < .001) correlated inversely with the Matsuda Index of insulin sensitivity, but not with percentage body fat. Aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), plasma AST, and alanine aminotransferase (ALT) all decreased significantly with triple therapy, but only the decrease in plasma AST and ALT correlated with the severity of steatosis and fibrosis at EOS. CONCLUSIONS: At EOS, subjects with type 2 diabetes treated with triple therapy had less hepatic steatosis and fibrosis versus conventional therapy; the severity of hepatic steatosis and fibrosis were both strongly and inversely correlated with insulin resistance; and changes in liver fibrosis scores (APRI, NFS, Fibrosis-4, and AST/ALT ratio) have limited value in predicting response to therapy.

Restriction Spectrum Imaging-Magnetic Resonance Imaging to Improve Prostate Cancer Imaging in Men on Active Surveillance.

PURPOSE: Restriction spectrum imaging-magnetic resonance imaging is a short duration enhanced diffusion-weighted technique that seeks to standardize sequences and predict upgrading. We test this technology for active surveillance biopsies. Our objective is to investigate the utility of restriction spectrum imaging-magnetic resonance imaging to improve upgrading detection in a prostate cancer active surveillance cohort. MATERIALS AND METHODS: We prospectively enrolled men on active surveillance undergoing repeat biopsy from January 2016 to June 2019. Subjects underwent prostate multiparametric magnetic resonance imaging and restriction spectrum imaging-magnetic resonance imaging reviewed by a urological radiologist for PI-RADS® scored lesions, followed by magnetic resonance imaging-guided prostate biopsy by a urologist. Restriction spectrum imaging-magnetic resonance imaging analysis with proprietary research software (CorTechs Labs, San Diego, California) generated a restricted signal map. We compared the restricted signal map and apparent diffusion coefficient values using T-test, ANOVA, and logistic regression analyses for prediction of upgrading. RESULTS: Of 123 enrolled men we identified 74 restriction spectrum imaging-magnetic resonance imaging regions of interest (targeted lesions) in 110 subjects, with 105 subjects completing biopsy. The restricted signal map was significant per PI-RADS score for true-positive lesion detection (mean difference 28, SD 0.7, p=0.001), and better than apparent diffusion coefficient (mean difference -15, SD 55, p=0.6). Restriction spectrum imaging generated restricted signal map values >50 improved sensitivity, specificity, positive predictive value and negative predictive value (81.0%, 81.8%, 54.2% and 94.2%) over PI-RADS ≥3 (71.4%, 38.9%, 23.7% and 83.7%, respectively) for Gleason upgrading. Overall restriction spectrum imaging is able to improve the AUC of 0.70 (95% CI 0.49-0.92, p=0.03) to 0.90 (95% CI 0.82-0.98, p <0.001). CONCLUSIONS: Restriction spectrum imaging-magnetic resonance imaging enhances the standard PI-RADS system by providing a noninvasive radiological biomarker to predict upgrading in active surveillance.

Computational Modeling of Human Left Ventricle to Assess the Effects of Trabeculae Carneae on the Diastolic and Systolic Functions.

Trabeculae carneae are irregular structures that cover the endocardial surfaces of both ventricles and account for a significant portion of human ventricular mass. The role of trabeculae carneae in diastolic and systolic functions of the left ventricle (LV) is not well understood. Thus, the objective of this study was to investigate the functional role of trabeculae carneae in the LV. Finite element (FE) analyses of ventricular functions were conducted for three different models of human LV derived from high-resolution magnetic resonance imaging (MRI). The first model comprised trabeculae carneae and papillary muscles, while the second model had papillary muscles and partial trabeculae carneae, and the third model had a smooth endocardial surface. We customized these patient-specific models with myofiber architecture generated with a rule-based algorithm, diastolic material parameters of Fung strain energy function derived from biaxial tests and adjusted with the empirical Klotz relationship, and myocardial contractility constants optimized for average normal ejection fraction (EF) of the human LV. Results showed that the partial trabeculae cutting model had enlarged end-diastolic volume (EDV), reduced wall stiffness, and even increased end-systolic function, indicating that the absence of trabeculae carneae increased the compliance of the LV during diastole, while maintaining systolic function.

Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.).

KEY POINTS: Life course changes in cardiovascular function in a non-human primate have been comprehensively characterized. Age-related declines in normalized left ventricular stroke volume and cardiac output were found with corresponding decreases in biventricular ejection fractions and filling rates. There were age-related decreases in male and female baboon normalized left ventricular myocardial mass index, which declined at similar rates. Systolic functional declines in right ventricular function were observed with age, similar to the left ventricle. Sex differences were found in the rates and directions of right ventricular volume changes along with decreased end-systolic right ventricular sphericity. The results validate the baboon as an appropriate model for translational studies of cardiovascular functional decline with ageing. ABSTRACT: Previous studies reported cardiac function declines with ageing. This study determined changes in biventricular cardiac function in a well-characterized baboon model. Cardiac magnetic resonance imaging measured key biventricular parameters in 47 baboons (22 female, age 4-23 years). ANCOVA assessed sex and age changes with P < 0.05 deemed significant. Stroke volume, cardiac output and other cardiac functional parameters were normalized to body surface area. There were similar, age-related rates of decrease in male (M) and female (F) normalized left ventricular (LV) myocardial mass index (M: -1.2 g m-2  year-1 , F: -0.9 g m-2  year-1 ). LV ejection fraction declined at -0.96% year-1 (r = -0.43, P = 0.002) and right ventricular (RV) ejection fraction decreased at -1.2% year-1 (r = -0.58, P < 0.001). Normalized LV stroke volume fell at -1.1 ml m-2  year-1 (r = -0.47, P = 0.001), normalized LV ejection rate at -3.8 ml s-1  m-2  year-1 (r = -0.43, P < 0.005) and normalized LV filling rate at -4.1 ml s-1  m-2  year-1 (r = -0.44, P < 0.005). Also, RV wall thickening fraction decreased with age (slope = -1% year-1 , P = 0.008). RV ejection rate decreased at -3.6 ml s-1  m-2  year-1 (P = 0.002) and the normalized average RV filling rate dropped at -3.7 ml s-1  m-2  year-1 (P < 0.0001). End-systolic RV sphericity index also dropped with age (r = -0.33, P = 0.02). Many observed changes parallel previously reported data in human and animal studies. These measured biventricular functional declines in hearts with ageing from the closest experimental primate species to man underscore the utility of the baboon model for investigating mechanisms related to heart ageing.

Intrauterine growth restriction results in persistent vascular mismatch in adulthood.

KEY POINTS: Intrauterine growth restriction (IUGR) increases offspring risk of chronic diseases later in life, including cardiovascular dysfunction. Our prior studies suggest biventricular cardiac dysfunction and vascular impairment in baboons who were IUGR at birth because of moderate maternal nutrient reduction. The current study reveals changes in artery sizes, distensibility, and blood flow pattern in young adult IUGR baboons, which may contribute to cardiac stress. The pattern of abnormality observed suggests that vascular redistribution seen with IUGR in fetal life may continue into adulthood. ABSTRACT: Maternal nutrient reduction induces intrauterine growth restriction (IUGR), increasing risks of chronic diseases later in life, including cardiovascular dysfunction. Using ultrasound, we determined regional blood flow, blood vessel sizes, and distensibility in IUGR baboons (8 males, 8 females, 8.8 years, similar to 35 human years) and controls (12 males, 12 females, 9.5 years). The measured blood vessels were larger in size in the males compared to females before but not after normalization to body surface area. Smaller IUGR normalized blood vessel sizes were observed in the femoral and external iliac arteries but not the brachial or common carotid arteries and not correlated significantly with birth weight. Mild decrease in distensibility in the IUGR group was seen in the iliac but not the carotid arteries without between-sex differences. In IUGR baboons there was increased carotid arterial blood flow velocity during late systole and diastole. Overall, our findings support the conclusion that region specific vascular and haemodynamic changes occur with IUGR, which may contribute to the occurrence of later life cardiac dysfunction. The pattern of alteration observed suggests vascular redistribution efforts in response to challenges in the perinatal period may persist into adulthood. Further studies are needed to determine the life course progression of these changes.

Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study.

Mitochondrial function has been examined in insulin-resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in T2DM reported results as relative concentrations of metabolite ratios, which could obscure differences in phosphocreatine ([PCr]) and adenosine triphosphate concentrations ([ATP]) between T2DM and normal glucose tolerance (NGT) individuals. We used an image-guided 31P-MRS method to quantitate [PCr], inorganic phosphate [Pi], phosphodiester [PDE], and [ATP] in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects also received oral glucose tolerance test, euglycemic insulin clamp, 1H-MRS to measure intramyocellular lipids [IMCL], and VL muscle biopsy to evaluate mitochondrial density. T2DM subjects had lower absolute [PCr] and [ATP] than NGT subjects (PCr 28.6 ± 3.2 vs. 24.6 ± 2.4, P < 0.002, and ATP 7.18 ± 0.6 vs. 6.37 ± 1.1, P < 0.02) while [PDE] was higher, but not significantly. [PCr], obtained using the traditional ratio method, showed no significant difference between groups. [PCr] was negatively correlated with HbA1c ( r = -0.63, P < 0.01) and fasting plasma glucose ( r = -0.51, P = 0.01). [PDE] was negatively correlated with Matsuda index ( r = -0.43, P = 0.03) and M/I ( r = -0.46, P = 0.04), but was positively correlated with [IMCL] ( r = 0.64, P < 0.005), HbA1c, and FPG ( r = 0.60, P = 0.001). To summarize, using a modified, in vivo quantitative 31P-MRS method, skeletal muscle [PCr] and [ATP] are reduced in T2DM, while this difference was not observed with the traditional ratio method. The strong inverse correlation between [PCr] vs. HbA1c, FPG, and insulin sensitivity supports the concept that lower baseline skeletal muscle [PCr] is related to key determinants of glucose homeostasis.

Sex-dimorphic acceleration of pericardial, subcutaneous, and plasma lipid increase in offspring of poorly nourished baboons.

Developmental programming by reduced maternal nutrition alters function in multiple offspring physiological systems, including lipid metabolism. We have shown that intrauterine growth restriction (IUGR) leads to offspring cardiovascular dysfunction with an accelerated aging phenotype in our nonhuman primate, baboon model. We hypothesized age-advanced pericardial fat and blood lipid changes. In pregnancy and lactation, pregnant baboons ate ad lib (control) or 70% ad lib diet (IUGR). We studied baboon offspring pericardial lipid deposition with magnetic resonance imaging at 5-6 years (human equivalent 20-24 years), skinfold thickness, and serum lipid profile at 8-9 years (human equivalent 32-36 years), comparing values with a normative life-course baboon cohort, 4-23 years. Increased pericardial fat deposition occurred in IUGR males but not females. Female but not male total cholesterol, low-density lipoprotein, and subcutaneous fat were increased with a trend of triglycerides increase. When comparing IUGR changes to values in normal older baboons, the increase in male apical pericardial fat was equivalent to advancing age by 6 years and the increase in female low-density lipoprotein to an increase of 3 years. We conclude that reduced maternal diet accelerates offspring lipid changes in a sex-dimorphic manner. The interaction between programming and accelerated lipogenesis warrants further investigation.

Efficacy and safety of antenatal steroids.

Antenatal steroids (ANS) are among the most important and widely utilized interventions to improve outcomes for preterm infants. A significant body of evidence demonstrates improved outcomes in preterm infants (24-34 wk) delivered between 1 and 7 days after the administration of a single course of ANS. Moreover, ANS have the advantage of being widely available, low cost, and easily administered via maternal intramuscular injection. The use of ANS to mature the fetal lung is, however, not without contention. Their use in pregnancy is not FDA approved, and treatment doses and regimens remain largely unoptimized. Their mode of use varies considerably between countries, and there are lingering concerns regarding the safety of exposing the fetus to high doses of exogenous steroids. A significant proportion of women deliver outside the 1- to 7-day therapeutic window after ANS treatment, and this delay may be associated with an increased risk of adverse outcomes for both mother and baby. Today, animal-based studies are one means by which key questions of dosing and safety relating to ANS may be resolved, allowing for further refinement(s) of this important therapy. Complementary approaches using nonhuman primates, sheep, and rodents have provided invaluable advances to our understanding of how exogenous steroid exposure impacts fetal development. Focusing on these three major model groups, this review highlights the role of three key animal models (sheep, nonhuman primates, rodents) in the development of antenatal steroid therapy, and provides an up-to-date synthesis of current efforts to refine this therapy in an era of personalised medicine.

Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

KEY POINTS: Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. ABSTRACT: Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction.

Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons.

KEY POINTS: Maternal nutrient restriction induces intrauterine growth restriction (IUGR) and leads to heightened cardiovascular risks later in life. We report right ventricular (RV) filling and ejection abnormalities in IUGR young adult baboons using cardiac magnetic resonance imaging. Both functional and morphological indicators of poor RV function were seen, many of which were similar to effects of ageing, but also with a few key differences. We observed more pronounced RV changes compared to our previous report of the left ventricle, suggesting there is likely to be a component of isolated RV abnormality in addition to expected haemodynamic sequelae from left ventricular dysfunction. In particular, our findings raise the suspicion of pulmonary hypertension after IUGR. This study establishes that IUGR also leads to impairment of the right ventricle in addition to the left ventricle classically studied. ABSTRACT: Maternal nutrient restriction induces intrauterine growth restriction (IUGR), increasing later life chronic disease including cardiovascular dysfunction. Our left ventricular (LV) CMRI studies in IUGR baboons (8 M, 8 F, 5.7 years - human equivalent approximately 25 years), control offspring (8 M, 8 F, 5.6 years), and normal elderly (OLD) baboons (6 M, 6 F, mean 15.9 years) revealed long-term LV abnormalities in IUGR offspring. Although it is known that right ventricular (RV) function is dependent on LV health, the IUGR right ventricle remains poorly studied. We examined the right ventricle with cardiac magnetic resonance imaging in the same cohorts. We observed decreased ejection fraction (49 ± 2 vs. 33 ± 3%, P < 0.001), cardiac index (2.73 ± 0.27 vs. 1.89 ± 0.20 l min-1 m-2 , P < 0.05), early filling rate/body surface area (BSA) (109.2 ± 7.8 vs. 44.6 ± 7.3 ml s-1  m-2 , P < 0.001), wall thickening (61 ± 3 vs. 44 ± 5%, P < 0.05), and longitudinal shortening (26 ± 3 vs. 15 ± 2%, P < 0.01) in IUGR animals with increased chamber volumes. Many, but not all, of these changes share similarities to normal older animals. Our findings suggest IUGR-induced pulmonary hypertension should be further investigated and that atrial volume, pulmonic outflow and interventricular septal motion may provide valuable insights into IUGR cardiovascular physiology. Overall, our findings reaffirm that gestational and neonatal challenges can result in long-term programming of poor offspring cardiovascular health. To our knowledge, this is the first study reporting IUGR-induced programmed adult RV dysfunction in an experimental primate model.

Characterization of atherosclerotic plaque: a contrast-detail study using multidetector and cone-beam computed tomography.

A Hindmarsh-Rose model perceptibility phantom containing inserts with various in vitro atherosclerotic plaque compositions was constructed and imaged on a clinical 64 slice multidetector (MDCT) system using 80 and 120 kVp settings and two other cone-beam (CBCT) systems at 80 kVp. Perceptibility of the simulated lipid-fibrotic plaque solutions in the images was evaluated by six observers. The effective doses of the protocols employed were estimated using phantom CTDI-vol measurements placed at identical settings. The CBCT system allowed reduction in effective dose in comparison with the conventional MDCT system for imaging of the carotid plaque phantoms without degrading image quality. The CBCT dose was less than MDCT, with a mean dose of 1.14 ± 0.01 mSv and 1.11 ± 0.02 mSv for MDCT using two measuring techniques vs. 0.35 ± 0.01 mSv for CBCT. The image quality analysis showed no significant differences in the contrast-detail (C-D) curves of the best performing CBCT vs. clinical MDCT (p > 0.05) using a Mann-Whitney U test. Results indicate that low-tube-potential CBCT may produce comparable C-D resolution for phantom-based representations of soft plaque types with respect to MDCT systems. This study suggests that the utility of low kVp CT techniques for evaluating carotid vulnerable atherosclerotic plaque merits further study.

Essentials and guidelines for clinical medical physics residency training programs: executive summary of AAPM Report Number 249.

There is a clear need for established standards for medical physics residency training. The complexity of techniques in imaging, nuclear medicine, and radiation oncology continues to increase with each passing year. It is therefore imperative that training requirements and competencies are routinely reviewed and updated to reflect the changing environment in hospitals and clinics across the country. In 2010, the AAPM Work Group on Periodic Review of Medical Physics Residency Training was formed and charged with updating AAPM Report Number 90. This work group includes AAPM members with extensive experience in clinical, professional, and educational aspects of medical physics. The resulting report, AAPM Report Number 249, concentrates on the clinical and professional knowledge needed to function independently as a practicing medical physicist in the areas of radiation oncology, imaging, and nuclear medicine, and constitutes a revision to AAPM Report Number 90. This manuscript presents an executive summary of AAPM Report Number 249.

Prostate MRI for the detection of clinically significant prostate cancer: Update and future directions.

PURPOSE OF REVIEW: In recent decades, there has been an increasing role for magnetic resonance imaging (MRI) in the detection of clinically significant prostate cancer (csPC). The purpose of this review is to provide an update and outline future directions for the role of MRI in the detection of csPC. RECENT FINDINGS: In diagnosing clinically significant prostate cancer pre-biopsy, advances include our understanding of MRI-targeted biopsy, the role of biparametric MRI (non-contrast) and changing indications, for example the role of MRI in screening for prostate cancer. Furthermore, the role of MRI in identifying csPC is maturing, with emphasis on standardization of MRI reporting in active surveillance (PRECISE), clinical staging (EPE grading, MET-RADS-P) and recurrent disease (PI-RR, PI-FAB). Future directions of prostate MRI in detecting csPC include quality improvement, artificial intelligence and radiomics, positron emission tomography (PET)/MRI and MRI-directed therapy. SUMMARY: The utility of MRI in detecting csPC has been demonstrated in many clinical scenarios, initially from simply diagnosing csPC pre-biopsy, now to screening, active surveillance, clinical staging, and detection of recurrent disease. Continued efforts should be undertaken not only to emphasize the reporting of prostate MRI quality, but to standardize reporting according to the appropriate clinical setting.

Metabolic Diaschisis in Mild Traumatic Brain Injury.

Neurophysiological diaschisis presents in traumatic brain injury (TBI) as functional impairment distant to the lesion site caused by axonal neuroexcitation and deafferentation. Diaschisis studies in TBI models have evaluated acute phase functional and microstructural changes. Here, in vivo biochemical changes and cerebral blood flow (CBF) dynamics following TBI are studied with magnetic resonance. Behavioral assessments, magnetic resonance spectroscopy (MRS), and CBF measurements on rats followed cortical impact TBI. Data were acquired pre-TBI and 1-3 h, 2-days, 7-days, and 14-days post-TBI. MRS was performed on the ipsilateral and contralateral sides in the cortex, striatum, and thalamus. Metabolites measured by MRS included N-acetyl aspartate (NAA), aspartate (Asp), lactate (Lac), glutathione (GSH), and glutamate (Glu). Lesion volume expanded for 2 days post-TBI and then decreased. Ipsilateral CBF dropped acutely versus baseline on both sides (-62% ipsilateral, -48% contralateral, p < 0.05) but then recovered in cortex, with similar changes in ipsilateral striatum. Metabolic changes versus baseline included increased Asp (+640% by Day 7 post-TBI, p < 0.05) and Lac (+140% on Day 2 post-TBI, p < 0.05) in ipsilateral cortex, while GSH (-67% acutely, p < 0.05) and NAA decreased (-50% on Day 2, p < 0.05). In contralateral cortex Lac decreased (-73% acutely, p < 0.05). Analysis of variance showed significance for Side (p < 0.05), Time after TBI (p < 0.05), and interactions (p < 0.005) for Asp, GSH, Lac, and NAA. Transient decreases of GSH (-30%, p < 0.05, acutely) and NAA (-23% on Day 2, p < 0.05) occurred in ipsilateral striatum with reduced GSH (-42%, p < 0.005, acutely) in the contralateral striatum. GSH was decreased in ipsilateral thalamus (-59% ipsilateral on Day 2, p < 0.05). Delayed increases of total choline were seen in the contralateral thalamus were noted as well (+21% on Day 7 post-TBI, p < 0.05). Both CBF and neurometabolite concentration changes occurred remotely from the TBI site, both ipsilaterally and contralaterally. Decreased Lac levels on the contralateral cortex following TBI may be indicative of reduced anaerobic metabolism during the acute phase. The timing and locations of the changes suggest excitatory and inhibitory signaling processes are affecting post-TBI metabolic fluctuations.

Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation via Hexosamine Biosynthetic Pathway.

Age is a prominent risk factor for cardiometabolic disease, often leading to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction exclusively resulting from physiological aging remain elusive. Previous research demonstrated age-related functional alterations in baboons, analogous to humans. The goal of this study is to identify early cardiac molecular alterations preceding functional adaptations, shedding light on the regulation of age-associated changes. Unbiased transcriptomics of left ventricle samples are performed from female baboons aged 7.5-22.1 years (human equivalent ≈30-88 years). Weighted-gene correlation network and pathway enrichment analyses are performed, with histological validation. Modules of transcripts negatively correlated with age implicated declined metabolism-oxidative phosphorylation, tricarboxylic acid cycle, glycolysis, and fatty-acid ß-oxidation. Transcripts positively correlated with age suggested a metabolic shift toward glucose-dependent anabolic pathways, including hexosamine biosynthetic pathway (HBP). This shift is associated with increased glycosaminoglycan synthesis, modification, precursor synthesis via HBP, and extracellular matrix accumulation, verified histologically. Upregulated extracellular matrix-induced signaling coincided with glycosaminoglycan accumulation, followed by cardiac hypertrophy-related pathways. Overall, these findings revealed a transcriptional shift in metabolism favoring glycosaminoglycan accumulation through HBP before cardiac hypertrophy. Unveiling this metabolic shift provides potential targets for age-related cardiac diseases, offering novel insights into early age-related mechanisms.

Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders.

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.