Hernan Jara

Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial.

CONTEXT Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterones effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood. OBJECTIVE To determine whether testosterones effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2). DESIGN, SETTING, AND PATIENTS The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010. INTERVENTIONS Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups). MAIN OUTCOME MEASURES The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels. RESULTS A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups. CONCLUSION Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00493987.

MR imaging of soft tissues adjacent to orthopaedic hardware: Techniques to minimize susceptibility artefact

This article demonstrates and compares imaging of orthopaedic hardware (fixation plates, screws, Kischner wire and prostheses) using gradient-echo, spin-echo and fast spin-echo sequences. It describes simple techniques which minimize susceptibility artefact induced by these components at magnetic resonance (MR) imaging, allowing visualization of adjacent soft tissues. The article emphasizes the importance of selecting the appropriate imaging plane in order to avoid hardware distortion of slice select gradients, emphasizes the importance of selecting frequency encoding gradient axes in order to orientate the long axis of the artefact away from the tissue of interest and, finally, compares the marked susceptibility artefact observed adjacent to hardware using gradient-echo with the artefact reduction achieved by using fast spin-echo sequences.

Voxel sensitivity function description of flow-induced signal loss in MR imaging: implications for black-blood MR angiography with turbo spin-echo sequences.

The conditions in which the image intensity of vessels transporting laminar flow is attenuated in black‐blood MR angiography (BB‐MRA) with turbo spin‐echo (TSE) and conventional spin‐echo (CSE) pulse sequences are investigated experimentally with a flow phantom, studied theoretically by means of a Bloch equation‐voxel sensitivity function (VSF) formalism, and computer modeled. The experiments studied the effects of: a) flow velocity, b) imaging axes orientation relative to the flow direction, and c) phase encoding order of the TSE train. The formulated Bloch equation‐VSF theory describes flow effects in two‐dimensional (2D)‐ and 3D‐Fourier transform magnetic resonance imaging. In this theoretical framework, the main attenuation mechanism instrumental to BB‐MRA, i.e., transverse magnetization dephasing caused by flow in the presence of the imaging gradients, is described in terms of flow‐induced distortions of the individual voxel sensitivity functions. The computer simulations predict that the intraluminal homogeneity and extent of flow‐induced image intensity attenuation increase as a function of decreasing vessel diameter, in support of the superior image quality achieved with TSE‐based BB‐MRA in the brain. Magn Reson Med 41:575–590, 1999.

Relaxo-volumetric multispectral quantitative magnetic resonance imaging of the brain over the human lifespan: global and regional aging patterns

The objective of this study was to determine the T1, T2 and secular-T2 relaxo-volumetric brain aging patterns using multispectral quantitative magnetic resonance imaging, both globally and regionally, and covering an age range approaching the full human lifespan. Fifty-one subjects (28 males, 23 females; age range: 0.5-87 years) were studied consisting of 18 healthy volunteers and 33 patients. Patients were selected after carefully reviewing their radiology reports to have either normal-by-MRI findings (25 patient subjects) or small focal pathology less than 6 mm in size (eight patient subjects). All subjects were MR imaged at 1.5 T with the mixed turbo spin echo pulse sequence. The soft tissues inside the cranial vault, termed intracranial matter (ICM), were segmented using a dual-clustering segmentation algorithm. ICM segments were further divided into six subsegments: bilateral anterior cerebral, posterior cerebral and cerebellar subsegments. T1, T2 and secular-T2 relaxation time histograms of all segments were generated and modeled with Gaussian functions. For each segment, the volumes of white matter, gray matter and cerebrospinal fluid were calculated from the T1 histograms. The age-related tendencies of three quantitative MRI parameters (T1, T2 and secular-T2) and the fractional tissue volumes showed four distinct periods of life, specifically a maturation period (0-2 years), a development period (2-20 years), an adulthood period (20-60 years) and a senescence period (60 years and older). For all ages, the anterior cerebral subsegment exhibited consistently longer gray matter T1s and shorter white matter T1s than the posterior cerebral and cerebellar subsegments. Volumetric age-related changes of the cerebellar subsegment were more gradual than in the cerebral subsegments. This study shows that relaxometric and volumetric age-related changes are synchronized and define the same four periods of brain evolution both globally and regionally.

Volumetric and semiquantitative assessment of MRI-detected subchondral bone marrow lesions in knee osteoarthritis: a comparison of contrast-enhanced and non-enhanced imaging.

OBJECTIVE Aim was to compare volumetric and semi-quantitative (SQ) measurements of subchondral bone marrow lesions (BMLs) on non-fat-suppressed (FS) T1-weighted (w), T1-w FS contrast enhanced (CE) and proton density (PD)-w FS images in order to define which sequence depicts the lesions to their maximum extent and if T1-w FS CE images and PD-w FS images may be used interchangeably to assess BMLs in a volumetric or SQ fashion. DESIGN Thirty-two patients with clinical knee osteoarthritis (OA) were scanned on a standard 1.5 T MRI system. A total of 47 BMLs were identified and were manually segmented on all three sequences. BMLs were also assessed semiquantitatively using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The volumetric and SQ results were compared across the three imaging sequences using paired t-tests. RESULTS Eighty-three percent of the lesions appeared largest on the PD-w FS sequence. Significant differences were observed for volumetric measurements between all three sequences (P < 0.001), however the mean volume difference between PD-w FS and T1-w FS CE (38%) was much smaller than for non-FS T1-w and PD-w FS/T1-w FS CE sequences (195% and 114%, respectively). Significant differences in WORMS scores were noted between PD-w FS and non-FS T1-w images and between T1-w FS CE and non-FS T1-w images (P < 0.001), but no significant difference was observed between PD-w FS and T1-w FS CE images. CONCLUSION Our findings suggest that the T1-w FS CE and PD-w FS sequences may be interchangeably used for quantitative volumetric and SQ assessment of BMLs.

Neurocognitive and academic outcomes at age 10 years of extremely preterm newborns

BACKGROUND AND OBJECTIVE: Despite reductions in mortality and morbidity among children born extremely preterm, they remain at high risk of neurocognitive deficits, with up to 40% having significant cognitive deficits at school age. We assessed the rate of neurocognitive impairment in a contemporary US cohort of 873 children aged 10 years who were born <28 weeks’ gestation. METHODS: The families of 889 of 966 (92%) children enrolled from 2002 to 2004 at 14 sites in 5 states returned at age 10 years for a comprehensive assessment of IQ, language, attention, executive function, processing speed, visual perception, visual-motor function, and academic achievement. RESULTS: A total of 873 children were assessed with well-validated tests of cognitive and academic function. Distributions of test scores were consistently and markedly shifted below normative expectation, with one-third to two-thirds of children performing >1 SD below age expectation. The most extreme downward shifts were on measures of executive control and processing speed. Multivariate analyses, adjusted for socioeconomic status, growth restriction, and other potential confounders, revealed that the risk of poor outcome was highest at the lowest gestational age across all 18 measures. CONCLUSIONS: More than half of our extremely preterm cohort exhibited moderate or severe neurocognitive deficits at age 10 years, with the most extensive impairments found among those born at the lowest gestational age. Children born extremely preterm continue to be at significant risk of persistent impairments in neurocognitive function and academic achievement, underscoring the need for monitoring and remediating such outcomes beginning in early childhood.

Differentiation of hepatocellular carcinoma and hepatic metastasis from cysts and hemangiomas with calculated T2 relaxation times and the T1/T2 relaxation times ratio

To determine the diagnostic capability of the T1 and T2 relaxation times and the T1/T2 relaxation times ratio generated with the mixed turbo spin echo (mixed‐TSE) pulse sequence, in order to discriminate between hepatocellular carcinoma (HCC)/metastases and hemangiomas/cysts.

Characterizing non‐gaussian, high b‐value diffusion in liver fibrosis: Stretched exponential and diffusional kurtosis modeling

To employ the stretched exponential and diffusional kurtosis models to study the non‐Gaussian behavior of diffusion‐related signal decay of the liver in an animal model of hepatic fibrosis.

The Relationship of Ectopic Lipid Accumulation to Cardiac and Vascular Function in Obesity and Metabolic Syndrome

Storage of lipid in ectopic depots outside of abdominal visceral and subcutaneous stores, including within the pericardium and liver, has been associated with obesity, insulin resistance, and cardiovascular risk. We sought to determine whether anatomically distinct ectopic depots were physiologically correlated and site‐specific effects upon cardiovascular function could be identified. Obese subjects (n = 28) with metabolic syndrome but without known atherosclerotic disease and healthy controls (n = 18) underwent magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) to quantify pericardial and periaortic lipid volumes, cardiac function, aortic compliance, and intrahepatic lipid content. Fasting plasma lipoproteins, glucose, insulin, and free‐fatty acids were measured. Pericardial and intrahepatic (P < 0.01) and periaortic (P < 0.05) lipid volumes were increased in obese subjects vs. controls and were strongly and positively correlated (P ≤ 0.01) but independent of BMI (P = NS) among obese subjects. Intrahepatic lipid was associated with insulin resistance (P < 0.01) and triglycerides (P < 0.05), whereas pericardial and periaortic lipid were not (P = NS). Periaortic and pericardial lipid positively correlated to free‐fatty acids (P ≤ 0.01) and negatively correlated to high‐density lipoprotein (HDL) cholesterol (P < 0.05). Pericardial lipid negatively correlated to cardiac output (P = 0.03) and stroke volume (P = 0.01) but not to left ventricular ejection fraction (P = 0.46). None of the ectopic depots correlated to aortic compliance. In conclusion, ectopic storage of lipid in anatomically distinct depots appeared tightly correlated but independent of body size. Site‐specific functional abnormalities were observed for pericardial but not periaortic lipid. These findings underscore the utility of MRI to assess individual differences in ectopic lipid that are not predictable from BMI.

Effect of disease progression on liver apparent diffusion coefficient values in a murine model of NASH at 11.7 tesla MRI

To evaluate the apparent diffusion coefficient (ADC) values of liver in a murine model of non‐alcoholic steatohepatitis using 11.7 Tesla (T) MRI.