Military-related mild traumatic brain injury: clinical characteristics, advanced neuroimaging, and molecular mechanisms.

Mild traumatic brain injury (mTBI) is a significant health burden among military service members. Although mTBI was once considered relatively benign compared to more severe TBIs, a growing body of evidence has demonstrated the devastating neurological consequences of mTBI, including chronic post-concussion symptoms and deficits in cognition, memory, sleep, vision, and hearing. The discovery of reliable biomarkers for mTBI has been challenging due to under-reporting and heterogeneity of military-related mTBI, unpredictability of pathological changes, and delay of post-injury clinical evaluations. Moreover, compared to more severe TBI, mTBI is especially difficult to diagnose due to the lack of overt clinical neuroimaging findings. Yet, advanced neuroimaging techniques using magnetic resonance imaging (MRI) hold promise in detecting microstructural aberrations following mTBI. Using different pulse sequences, MRI enables the evaluation of different tissue characteristics without risks associated with ionizing radiation inherent to other imaging modalities, such as X-ray-based studies or computerized tomography (CT). Accordingly, considering the high morbidity of mTBI in military populations, debilitating post-injury symptoms, and lack of robust neuroimaging biomarkers, this review (1) summarizes the nature and mechanisms of mTBI in military settings, (2) describes clinical characteristics of military-related mTBI and associated comorbidities, such as post-traumatic stress disorder (PTSD), (3) highlights advanced neuroimaging techniques used to study mTBI and the molecular mechanisms that can be inferred, and (4) discusses emerging frontiers in advanced neuroimaging for mTBI. We encourage multi-modal approaches combining neuropsychiatric, blood-based, and genetic data as well as the discovery and employment of new imaging techniques with big data analytics that enable accurate detection of post-injury pathologic aberrations related to tissue microstructure, glymphatic function, and neurodegeneration. Ultimately, this review provides a foundational overview of military-related mTBI and advanced neuroimaging techniques that merit further study for mTBI diagnosis, prognosis, and treatment monitoring.

Recommendations for Imaging Patients With Cardiac Implantable Electronic Devices (CIEDs).

Historically, the presence of cardiac implantable electronic devices (CIEDs), including pacemakers and implantable cardioverter defibrillators (ICDs), was widely considered an absolute contraindication to magnetic resonance imaging (MRI). The recent development of CIEDs with MR Conditional labeling, as well as encouraging results from retrospective studies and a prospective trial on the safety of MRI performed in patients with CIEDs without MR Conditional labeling, have led to a reevaluation of this practice. The purpose of this report is to provide a concise summary of recent developments, including practical guidelines that an institution could adopt for radiologists who choose to image patients with CIEDs that do not have MR Conditional labeling. This report was written on behalf of and approved by the International Society for Magnetic Resonance in Medicine (ISMRM) Safety Committee. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 1.

Highly efficient head-only magnetic field insert gradient coil for achieving simultaneous high gradient amplitude and slew rate at 3.0T (MAGNUS) for brain microstructure imaging.

PURPOSE: To develop a highly efficient magnetic field gradient coil for head imaging that achieves 200 mT/m and 500 T/m/s on each axis using a standard 1 MVA gradient driver in clinical whole-body 3.0T MR magnet. METHODS: A 42-cm inner diameter head-gradient used the available 89- to 91-cm warm bore space in a whole-body 3.0T magnet by increasing the radial separation between the primary and the shield coil windings to 18.6 cm. This required the removal of the standard whole-body gradient and radiofrequency coils. To achieve a coil efficiency ~4× that of whole-body gradients, a double-layer primary coil design with asymmetric x-y axes, and symmetric z-axis was used. The use of all-hollow conductor with direct fluid cooling of the gradient coil enabled ≥50 kW of total heat dissipation. RESULTS: This design achieved a coil efficiency of 0.32 mT/m/A, allowing 200 mT/m and 500 T/m/s for a 620 A/1500 V driver. The gradient coil yielded substantially reduced echo spacing, and minimum repetition time and echo time. In high b = 10,000 s/mm2 diffusion, echo time (TE) < 50 ms was achieved (>50% reduction compared with whole-body gradients). The gradient coil passed the American College of Radiology tests for gradient linearity and distortion, and met acoustic requirements for nonsignificant risk operation. CONCLUSIONS: Ultra-high gradient coil performance was achieved for head imaging without substantial increases in gradient driver power in a whole-body 3.0T magnet after removing the standard gradient coil. As such, any clinical whole-body 3.0T MR system could be upgraded with 3-4× improvement in gradient performance for brain imaging.

Hemodynamic Effects of Late Sodium Current Inhibitors in a Swine Model of Heart Failure.

OBJECTIVES: To evaluate possible treatment-related hemodynamic changes, we administered ranolazine or mexiletine to swine with heart failure (HF) and to controls. BACKGROUND: Ranolazine and mexiletine potently inhibit depolarizing late Na+ current (INa,late) and Na+ entry into cardiomyocytes. Blocking Na+ entry may increase forward-mode Na/Ca exchange and reduce cellular Ca+2 load, further compromising systolic contraction during HF. METHODS AND RESULTS: Anesthetized tachypaced HF swine received ranolazine (n = 9) or mexiletine (n = 7) as boluses, then as infusions; the same experiments were performed in 10 nonpaced controls. The swine with HF had characteristic elevated left ventricular end-diastolic pressure (LVEDP) and reduced maximal left ventricular pressure rise (+dP/dtmax) and left ventricular peak systolic pressure (LVSP). No significant change occurred after ranolazine dosing for any parameter: LVEDP, +dP/dtmax, LVSP, heart rate, maximal LV pressure fall rate (-dP/dtmax), or time constant for isovolumic relaxation. Similar results seen in additional swine with HF: 7 were given mexiletine, and 7 others were given ranolazine after a 27% rate decrement to maximize INa,late. Patch-clamped HF cardiomyocytes confirmed drug-induced INa,late blockade. CONCLUSIONS: Ranolazine or mexiletine blocking INa,late neither worsened nor improved hemodynamics during advanced HF. Although results must be clinically confirmed, they suggest inhibition of INa,late by ranolazine or mexiletine may not exacerbate HF in patients.

Cardiac Imaging Modalities and Appropriate Use.

Cardiovascular imaging with calcium scoring computed tomography (CT), coronary CT angiography (CCTA), and cardiac MRI (CMR) have advanced rapidly over recent years. These imaging modalities have increased in availability, accessibility, and clinical practicality due to technological advances allowing for significant radiation dose reduction for high-quality CCTA and for rapid and reliable imaging techniques in CMR. Hardware and software developments are continually increasing efficiency and accuracy of postprocessing. In the context of these rapidly developing imaging modalities, it is critical for ordering physicians and providers to be aware of the fundamentals of each modality, imaging challenges and appropriate use criteria.

Multiacquisition T1-mapping MRI during tidal respiration for quantification of myocardial T1 in swine with heart failure.

OBJECTIVE: The purpose of this article is to evaluate a free-breathing pulse sequence to quantify myocardial T1 changes in a swine model of tachycardia-induced heart failure. MATERIALS AND METHODS: Yorkshire swine were implanted with pacemakers and were ventricularly paced at 200 beats/min to induce heart failure. Animals were scanned twice with a 1.5-T MRI scanner, once at baseline and once at heart failure. A T1-mapping sequence was performed during tidal respiration before and 5 minutes after the administration of a gadolinium-chelate contrast agent. T1-mapping values were compared between the baseline and heart failure scans. The percentage of fibrosis of heart failure myocardial tissue was compared with similar left ventricular tissue from control animals using trichrome blue histologic analysis. RESULTS: In the study cohort, differences were found between the baseline and heart failure T1-mapping values before the administration of contrast agent (960 ± 96 and 726 ± 94 ms, respectively; p = 0.02) and after contrast agent administration (546 ± 180 and 300 ± 171 ms, respectively; p = 0.005). The animals with heart failure also had a difference histologically in the percentage of myocardial collagen compared with tissue from healthy control animals (control, 5.4% ± 1.0%; heart failure, 9.4% ± 1.6%; p < 0.001). CONCLUSION: The proposed T1-mapping technique can quantify diffuse myocardial changes associated with heart failure without the use of a contrast agent and without breath-holding. These T1 changes appear to be associated with increases in the percentage of myocardial collagen that in this study were not detected by traditional myocardial delayed enhancement imaging. T1 mapping may be a useful technique for detecting early but clinically significant myocardial fibrosis.

Flexible cardiac T1 mapping using a modified Look-Locker acquisition with saturation recovery.

A modified Look-Locker acquisition using saturation recovery (MLLSR) for breath-held myocardial T(1) mapping is presented. Despite its reduced dynamic range, saturation recovery enables substantially higher imaging efficiency than conventional inversion recovery T(1) mapping because it does not require time for magnetization to relax to equilibrium. Therefore, MLLSR enables segmented readouts, shorter data acquisition windows, and shorter breath holds compared with inversion recovery. T(1) measurements in phantoms using MLLSR showed a high correlation with conventional single-point inversion recovery spin echo. In vivo T(1) measurements from normal and infarcted myocardium in 41 volunteers and patients were consistent with previously reported values. Twenty subjects were also scanned with MLLSR using an accelerated sampling scheme that required half the scan time (eight vs. 16 heartbeats) but yielded equivalent results. The flexibility afforded by the improved imaging efficiency of MLLSR allows the acquisition to be tailored to particular clinical needs and to individual patient's breath-holding abilities.

A review of cohort study design for cardiovascular nursing research.

Nursing research encompasses a wide array of study areas that often times follow specific groups of patients or patient types. The cohort study design is a useful method to study any group, especially to track outcomes or to evaluate exposure or risk factors. Several different cohort study designs can be applied to the general population or to specific subpopulations or groups, such as those with cardiovascular disease. Cohort designs provide a temporal view of groups and exposures that can uncover outcomes and exposures that may be difficult to separate out in smaller, traditional experiments. There are several types of cohort designs, each with their unique advantages. Cohort designs may be prospective or retrospective. Although most cohort designs are longitudinal, there are also cross-sectional types of studies that are useful. As with any type of research design, selection of the study participants and control groups must be made carefully. It is important for the variables to be clearly defined and measurable. The investigator must also be aware of potential biases and weaknesses associated with different cohort study designs and account for these problems when they arise. Reports from cohort studies should be presented clearly, addressing the potential confounding problems. This article explores the many types of cohort designs, with examples from cardiovascular disease research to demonstrate how nurses can use this design in their research.

Simultaneous myocardial and fat suppression in magnetic resonance myocardial delayed enhancement imaging.

PURPOSE: To develop a method for fat suppression in myocardial delayed enhancement (MDE) studies that achieves effective signal intensity reduction in fat but does not perturb myocardial signal suppression. MATERIALS AND METHODS: A new approach to fat suppression that uses a spectrally-selective inversion-recovery (SPEC-IR) tip-up radio frequency (RF) pulse following the conventional nonselective IR RF pulse together with a second SPEC-IR RF pulse is proposed. The tip-up pulse restores the fat longitudinal magnetization after the nonselective IR pulse and allows the fat magnetization to recover more fully toward its equilibrium value, providing for better fat suppression by the second SPEC-IR RF pulse. This new approach was validated in phantom studies and in five patients. RESULTS: Effective fat suppression was achieved using the proposed technique with minimal impact on normal myocardial signal suppression. Mean fat suppression achieved using this approach was 67% +/- 8%, as measured in the chest wall immediately opposite the heart. CONCLUSION: The results indicate this modular-type approach optimizes fat suppression in myocardial delayed enhancement studies but does not perturb the basic IR pulse sequence or change basic acquisition parameters.

Computerized information management for institutional review boards.

The use of human subjects for medical research in most industrialized nations requires the scientific and ethical scrutiny of research proposals by a governing institutional review board (IRB) or its equivalent. As part of their primary charge to protect human subjects, IRBs are responsible for the regulatory oversight of not only the research protocol itself but also the research conduct of the investigators and, if applicable, the funding sponsor. This article will discuss the regulatory requirements for an accurate account of IRB protocols and investigators and present an overview of the general flow of information for an IRB protocol. The current and potential uses of information management systems by IRBs will also be reviewed and accompanied by a discussion of the potential advantages and disadvantages of various computerized information systems for management of clinical research.

Major vascular anomalies in Turner syndrome: prevalence and magnetic resonance angiographic features.

BACKGROUND: Turner syndrome (TS) is associated with aortic coarctation and dissection; hence, echocardiographic evaluation of all patients is currently recommended. X-ray angiography in clinically symptomatic patients has suggested a range of other vascular anomalies, but the true prevalence of such lesions in TS is unknown. To better understand the prevalence and pathogenesis of cardiovascular defects in TS, we prospectively evaluated a group of asymptomatic adult volunteers with TS using magnetic resonance (MR) angiography. METHODS AND RESULTS: A total of 85 adults with TS and 27 normal female adult volunteers underwent gadolinium-enhanced 3D MR angiography. A high prevalence of aortic anomalies was seen in women with TS, including elongation of the transverse arch (49%), aortic coarctation (12%), and aberrant right subclavian artery (8%). Venous anomalies were also prominent, including persistent left superior vena cava (13%) and partial anomalous pulmonary venous return (13%). None of these anomalies were found in healthy female controls. The constellation of elongation of the transverse arch, aortic coarctation, and persistent left superior vena cava was significantly associated with women with TS. Neck webbing and increased thoracic anterior-to-posterior dimension diameters were strong predictors for arterial and venous anomalies. CONCLUSIONS: Thoracic vascular anomalies are common in TS, occurring in approximately 50% of a group not preselected for cardiovascular disease. The highly significant association between neck webbing, increased chest diameter, and these vascular anomalies suggests that in utero, centrally localized lymphatic obstruction may contribute to these cardiovascular deformities in TS. Improved recognition of these often-undetected vascular lesions may be important for identification of patients in need of closer cardiovascular monitoring.

MRA of the thoracic vessels.

Magnetic resonance imaging (MRI) is well suited for the noninvasive evaluation of the thoracic vasculature, and with improvements in scanner technology, the ability of MR to illustrate the thoracic vessels has significantly improved. Dedicated vascular software and pulse sequences have become commercially available, and fast imaging, in particular, has facilitated the time-efficient and comprehensive MR evaluation of most thoracic vascular lesions. Over the years, a host of black and bright blood MRI methods have evolved into practical tools for illustration of the thoracic vessels. As with other MR applications, successful vascular depiction relies significantly on the proper selection and prescription of imaging pulse sequences. In this article, these methods with their specific technical and practical pitfalls for thoracic magnetic resonance angiography (MRA) will be discussed. Current clinical indications for thoracic MRA will also be illustrated.

High-resolution gadolinium-enhanced 3D MRA of the infrapopliteal arteries. Lessons for improving bolus-chase peripheral MRA.

Peripheral magnetic resonance angiography (MRA) is growing in use. However, methods of performing peripheral MRA vary widely and continue to be optimized, especially for improvement in illustration of infrapopliteal arteries. The main purpose of this project was to identify imaging factors that can improve arterial visualization in the lower leg using bolus chase peripheral MRA. Eighteen healthy adults were imaged on a 1.5T MR scanner. The calf was imaged using conventional three-station bolus chase three-dimensional (3D) MRA, two dimensional (2D) time-of-flight (TOF) MRA and single-station Gadolinium (Gd)-enhanced 3D MRA. Observer comparisons of vessel visualization, signal to noise ratios (SNR), contrast to noise ratios (CNR) and spatial resolution comparisons were performed. Arterial SNR and CNR were similar for all three techniques. However, arterial visualization was dramatically improved on dedicated, arterial-phase Gd-enhanced 3D MRA compared with the multi-station bolus chase MRA and 2D TOF MRA. This improvement was related to optimization of Gd-enhanced 3D MRA parameters (fast injection rate of 2 mL/sec, high spatial resolution imaging, the use of dedicated phased array coils, elliptical centric k-space sampling and accurate arterial phase timing for image acquisition). The visualization of the infrapopliteal arteries can be substantially improved in bolus chase peripheral MRA if voxel size, contrast delivery, and central k-space data acquisition for arterial enhancement are optimized. Improvements in peripheral MRA should be directed at these parameters.

MR angiography using steady-state free precession.

Contrast-enhanced MR angiography (CE-MRA) using steady-state free precession (SSFP) pulse sequences is described. Using SSFP, vascular structures can be visualized with high signal-to-noise ratio (SNR) at a substantial (delay) time after the initial arterial pass of contrast media. The peak blood SSFP signal was diminished by <20% 30 min after the initial administration of 0.2 mmol/kg of Gd-chelate. The proposed method allows a second opportunity to study arterial or venous structures with high image SNR and high spatial resolution. A mask subtraction scheme using spin echo SSFP-S(-) acquisition is also described to reduce stationary background signal from the delayed SSFP angiography images.

Renal masses: quantitative assessment of enhancement with dynamic MR imaging.

PURPOSE: To establish a quantitative magnetic resonance (MR) imaging contrast enhancement criterion for distinguishing cysts from solid renal lesions. MATERIALS AND METHODS: Regions of interest were measured in 74 patients with renal lesions evaluated by means of dynamic contrast material-enhanced MR imaging with serial breath-hold spoiled gradient-echo acquisitions. Sensitivity for renal tumors and specificity for renal cysts were established by using percentage of enhancement thresholds that varied between 5% and 35%. RESULTS: The mean percentage of enhancement at MR imaging for the 50 renal cysts was less than 5%; for the 50 renal tumors, it was 97% or higher. With use of a threshold percentage of enhancement of 15% and results obtained between 2 and 4 minutes after administration of contrast material, all malignancies (sensitivity for tumor, 100%) were diagnosed, and there were 6% or fewer false-positive tumor diagnoses. Lower thresholds resulted in unacceptably high false-positive rates (ie, cysts that appeared to enhance-pseudoenhancement), whereas higher threshold values (>20%) resulted in an unacceptably lower sensitivity for tumors. CONCLUSION: The optimal percentage of enhancement threshold for distinguishing cysts from malignancies with the imaging technique prescribed was 15%, and the optimal timing for measurement was 2-4 minutes after administration of contrast material.

Three-dimensional phase-contrast magnetic resonance angiography: a useful clinical adjunct to gadolinium-enhanced three-dimensional renal magnetic resonance angiography?

OBJECTIVE: To assess the value of three-dimensional (3D) phase-contrast (PC) magnetic resonance angiography (MRA) after gadolinium (Gd)-enhanced 3D MRA for renal artery imaging. METHODS: Twenty-one patients with suspected renal artery hypertension were reviewed. All studies included Gd-enhanced 3D MRA and 3D PC MRA. Blinded interpretation of the images was performed for each technique independently and in combination. Conventional X-ray angiography was used for diagnostic correlation when available. RESULTS: Renal artery stenosis was present in 7 (16.3%) of 43 renal arteries, confirmed by X-ray angiography. MRA images demonstrated 100% sensitivity and 74% specificity for Gd-enhanced 3D MRA and 100% sensitivity and 94% specificity for 3D PC MRA. All vessels were diagnosed correctly when both image sets were viewed. CONCLUSION: 3D PC MRA can improve the specificity of renal MRA by decreasing the number of false-positive Gd-enhanced 3D MRA interpretations.