Magnetic Resonance Imaging Approach Research Articles

Deep white matter in Huntington's disease.

White matter (WM) abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using Magnetic Resonance Imaging (MRI). In the present study, we examined the microstructure of the long-range large deep WM tracts by applying two different MRI approaches: Diffusion Tensor Imaging (DTI) -based tractography, and T2*weighted (iron sensitive) imaging. We collected Pre-HD subjects (n = 25), HD patients (n = 25) and healthy control subjects (n = 50). Results revealed increased axial (AD) and radial diffusivity (RD) and iron levels in Pre-HD subjects compared to controls. Fractional anisotropy decreased between the Pre-HD and HD phase and AD/RD increased and although impairment was pervasive in HD, degeneration occurred in a pattern in Pre-HD. Furthermore, iron levels dropped for HD patients. As increased iron levels are associated with remyelination, the data suggests that Pre-HD subjects attempt to repair damaged deep WM years before symptoms occur but this process fails with disease progression.

Ultrashort echo time magnetic resonance imaging of the lung using a high-relaxivity t1 blood-pool contrast agent.

The lung remains one of the most challenging organs to image using magnetic resonance imaging (MRI) due to intrinsic rapid signal decay. However, unlike conventional modalities such as computed tomography, MRI does not involve radiation and can provide functional and morphologic information on a regional basis. Here we demonstrate proof of concept for a new MRI approach to achieve substantial gains in a signal to noise ratio (SNR) in the lung parenchyma: contrast-enhanced ultrashort echo time (UTE) imaging following intravenous injection of a high-relaxivity blood-pool manganese porphyrin T1 contrast agent. The new contrast agent increased relative enhancement of the lung parenchyma by over 10-fold compared to gadolinium diethylene triamine pentaacetic acid (Gd-DTPA), and the use of UTE boosted the SNR by a factor of 4 over conventional T1-weighted gradient echo acquisitions. The new agent also maintains steady enhancement over at least 60 minutes, thus providing a long time window for obtaining high-resolution, high-quality images and the ability to measure a number of physiologic parameters.

Applications of in vivo imaging in the evaluation of the pathophysiology of viral and bacterial infections and in development of countermeasures to BSL3/4 pathogens.

While preclinical and clinical imaging have been applied to drug discovery/development and characterization of disease pathology, few examples exist where imaging has been used to evaluate infectious agents or countermeasures to biosafety level (BSL)3/4 threat agents. Viruses engineered with reporter constructs, i.e., enzymes and receptors, which are amenable to detection by positron emission tomography (PET), single photon emission tomography (SPECT), or magnetic resonance imaging (MRI) have been used to evaluate the biodistribution of viruses containing specific therapeutic or gene transfer payloads. Bioluminescence and nuclear approaches involving engineered reporters, direct labeling of bacteria with radiotracers, or tracking bacteria through their constitutively expressed thymidine kinase have been utilized to characterize viral and bacterial pathogens post-infection. Most PET, SPECT, CT, or MRI approaches have focused on evaluating host responses to the pathogens such as inflammation, brain neurochemistry, and structural changes and on assessing the biodistribution of radiolabeled drugs. Imaging has the potential when applied preclinically to the development of countermeasures against BSL3/4 threat agents to address the following: (1) presence, biodistribution, and time course of infection in the presence or absence of drug; (2) binding of the therapeutic to the target; and (3) expression of a pharmacologic effect either related to drug mechanism, efficacy, or safety. Preclinical imaging could potentially provide real-time dynamic tools to characterize the pathogen and animal model and for developing countermeasures under the U.S. FDA Animal Rule provision with high confidence of success and clinical benefit.

T2-Weighted MRI Detects Presymptomatic Pathology in the SOD1 Mouse Model of ALS

Neuroinflammation has been identified as a potential therapeutic target in amyotrophic lateral sclerosis (ALS), but relevant biomarkers are needed. The superoxide dismutase (SOD1)G93A transgenic mouse model of ALS offers a unique opportunity to study and potentially manipulate presymptomatic pathology. While T2-weighted magnetic resonance imaging (MRI) has been shown to be sensitive to pathologic changes at symptom onset, no earlier biomarkers were previously identified and the underlying histopathologic correlates remain uncertain. To address these issues, we used a multimodal MRI approach targeting structural (T2, T1, apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR)), vascular (gadolinium diethylene triamine pentaacetic acid), and endothelial (vascular cell adhesion molecule–microparticles of iron oxide) changes, together with histopathologic analysis from presymptomatic to symptomatic stages of disease. Presymptomatic changes in brainstem nuclei were evident on T2-weighted images from as early as 60 days (P<0.05). Histologic indices of vacuolation, astro- and microglial activation all correlated with T2-weighted changes. Significant reductions in ADC (P<0.01) and MTR (P<0.05) were found at 120 days in the same brainstem nuclei. No changes in T1 relaxation, vascular permeability, or endothelial activation were found at any stage of disease. These findings suggest that T2-weighted MRI offers the strongest biomarker potential in this model, and that MRI has unique potential for noninvasive and longitudinal assessment of presymptomatically applied therapeutic and neuroprotective agents.

Novel MRI and CT Approaches for the Characterization of Myocardial Infarct

Accurate myocardial viability assessment is essential to optimize revascularization and/or medical treatment in patients with myocardial infarct. To date, cardiac magnetic resonance imaging (MRI) is the widely accepted clinical standard for visualization, characterization and quantification of myocardial viability. Multidetector computed tomography (CT) is reported by numerous authors as an emerging imaging modality for myocardial viability assessment. This review article summarizes cardiac MRI and CT modalities for myocardial viability assessment.

Improved Contrast in Ultra-Low-Field MRI with Time-Dependent Bipolar Prepolarizing Fields: Theory and NMR Demonstrations

Abstract The spin-lattice (T1) relaxation rates of materials depend on the strength of the external magnetic field in which the relaxation occurs. This T1 dispersion has been suggested to offer a means to discriminate between healthy and cancerous tissue by performing magnetic resonance imaging (MRI) at low magnetic fields. In prepolarized ultra-low-field (ULF) MRI, spin precession is detected in fields of the order of 10-100 μT. To increase the signal strength, the sample is first magnetized with a relatively strong polarizing field. Typically, the polarizing field is kept constant during the polarization period. However, in ULF MRI, the polarizing-field strength can be easily varied to produce a desired time course. This paper describes how a novel variation of the polarizing-field strength and duration can optimize the contrast between two types of tissue having different T1 relaxation dispersions. In addition, NMR experiments showing that the principle works in practice are presented. The described procedure may become a key component for a promising new approach of MRI at ultra-low fields

Trends and clinical implications of preoperative breast MRI in Medicare beneficiaries with breast cancer

While there has been increasing interest in the use of preoperative breast magnetic resonance imaging (MRI) for women with breast cancer, little is known about trends in MRI use, or the association of MRI with surgical approach among older women. Using the Surveillance, Epidemiology and End Results-Medicare database, we identified a cohort of women diagnosed with breast cancer from 2000 to 2009 who underwent surgery. We used Medicare claims to identify preoperative breast MRI and surgical approach. We evaluated temporal trends in MRI use according to age and type of surgery, and identified factors associated with MRI. We assessed the association between MRI and surgical approach: breast-conserving surgery (BCS) versus mastectomy, bilateral versus unilateral mastectomy, and use of contralateral prophylactic mastectomy. Among the 72,461 women in our cohort, 10.1 % underwent breast MRI. Preoperative MRI use increased from 0.8 % in 2000-2001 to 25.2 % in 2008-2009 (p < 0.001). Overall, 43.3 % received mastectomy and 56.7 % received BCS. After adjustment for clinical and demographic factors, MRI was associated with an increased likelihood of having a mastectomy compared to BCS (adjusted odds ratio = 1.21, 95 % CI 1.14-1.28). Among women who underwent mastectomy, MRI was significantly associated with an increased likelihood of having bilateral cancer diagnosed (9.7 %) and undergoing bilateral mastectomy (12.5 %) compared to women without MRI (3.7 and 4.1 %, respectively, p < 0.001 for both). In conclusion, the use of preoperative breast MRI has increased substantially among older women with breast cancer and is associated with an increased likelihood of being diagnosed with bilateral cancer, and more invasive surgery.

Magnetic-resonance imaging of the human brain with an atomic magnetometer

Magnetic resonance imaging (MRI) is conventionally performed in very high fields, and this leads to some restrictions in applications. To remove such restrictions, the ultra-low field MRI approach has been proposed. Because of the loss of sensitivity, the detection methods based on superconducting quantum interference devices (SQUIDs) in a shielded room were used. Atomic magnetometers have similar sensitivity as SQUIDs and can also be used for MRI, but there are some technical difficulties to overcome. We demonstrate that MRI of the human brain can be obtained with an atomic magnetometer with in-plane resolution of 3 mm in 13 min.

MRI study of cerebral, retinal and choroidal blood flow responses to acute hypertension

Blood flow (BF) in many tissues is stable during significant fluctuations in systemic arterial blood pressure or perfusion pressure under normal conditions. The regulatory mechanisms responsible for this non-passive BF behavior include both local and neural control mechanisms. This study evaluated cerebral BF (CBF), retinal BF (RBF) and choroidal BF (ChBF) responses to acute blood pressure increases in rats using magnetic resonance imaging (MRI). A transient increase in blood pressure inside the MRI scanner was achieved by mechanically inflating a balloon catheter to occlude the descending aorta near the diaphragm. We verified the rat model of mechanical occlusion and MRI approach by first measuring blood-flow regulatory responses to changing BP in the brain under normoxia and hypercapnia where the phenomenon is well documented. Retinal and choroidal blood-flow responses to transient increased arterial pressure were then investigated. In response to an acute increase in blood pressure, RBF exhibited autoregulatory behavior and ChBF exhibited baroregulation similar to that seen in the cerebral circulation. This approach may prove useful to investigate retinal and choroidal vascular dysregulation in rat models of retinal diseases with suspected vascular etiology.

A choline derivate-modified nanoprobe for glioma diagnosis using MRI

Gadolinium (Gd) chelate contrast-enhanced magnetic resonance imaging (MRI) is a preferred method of glioma detection and preoperative localisation because it offers high spatial resolution and non-invasive deep tissue penetration. Gd-based contrast agents, such as Gd-diethyltriaminepentaacetic acid (DTPA-Gd, Magnevist), are widely used clinically for tumor diagnosis. However, the Gd-based MRI approach is limited for patients with glioma who have an uncompromised blood-brain barrier (BBB). Moreover, the rapid renal clearance and non-specificity of such contrast agents further hinders their prevalence. We present a choline derivate (CD)-modified nanoprobe with BBB permeability, glioma specificity and a long blood half-life. Specific accumulation of the nanoprobe in gliomas and subsequent MRI contrast enhancement are demonstrated in vitro in U87 MG cells and in vivo in a xenograft nude model. BBB and glioma dual targeting by this nanoprobe may facilitate precise detection of gliomas with an uncompromised BBB and may offer better preoperative and intraoperative tumor localization.

Clinical Classification and Prognosis of Patients with Multiple Sclerosis in Northern China

Objective: To study the clinical classification of multiple sclerosis (MS) by analyzing the features of the magnetic resonance imaging (MRI) on brain and spinal cord and surveying the natural history. Methods: MRI examination was conducted on 132 clinically diagnosed multiple sclerosis patients and their quality of life and disability rate were graded. Results: The general distribution of lesions in the nervous system was obtained. In northern China, relapsing-remitting MS (RRMS) by natural course classification and simple brain MS by lesion distribution classification lead to fewer neurological deficits with a relatively top life quality. Meanwhile, there is a tendency for the correlation between the pathogenetic locations of MS and its natural course prognosis. Conclusion: To improve the understanding of the prognosis of MS and promote the diagnosis ability to guide MS treatment. Multiple sclerosis (MS) is a common immune-mediated chronic disease of the central nervous system with the demyelination of white matter as the main pathological feature. The incidence of MS has a significant regional difference and studies on the natural history classification and lesions distribution classification of MS patients in northern China are not sufficient. In this study, natural history and lesions distribution of MS patients were classified by MRI approach and the impacts of each MS classification on neurological deficits and quality of life were observed. In this thesis, features and prognosis of MS classifications in northern China are discussed for the purpose of improving the level of diagnosis and treatment.

Diagnostic performance of a rapid magnetic resonance imaging method of measuring hepatic steatosis.

ObjectivesHepatic steatosis is associated with an increased risk of developing serious liver disease and other clinical sequelae of the metabolic syndrome. However, visual estimates of steatosis from histological sections of biopsy samples are subjective and reliant on an invasive procedure with associated risks. The aim of this study was to test the ability of a rapid, routinely available, magnetic resonance imaging (MRI) method to diagnose clinically relevant grades of hepatic steatosis in a cohort of patients with diverse liver diseases.Materials and MethodsFifty-nine patients with a range of liver diseases underwent liver biopsy and MRI. Hepatic steatosis was quantified firstly using an opposed-phase, in-phase gradient echo, single breath-hold MRI methodology and secondly, using liver biopsy with visual estimation by a histopathologist and by computer-assisted morphometric image analysis. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the MRI method against the biopsy observations.ResultsThe MRI approach had high sensitivity and specificity at all hepatic steatosis thresholds. Areas under ROC curves were 0.962, 0.993, and 0.972 at thresholds of 5%, 33%, and 66% liver fat, respectively. MRI measurements were strongly associated with visual (r2 = 0.83) and computer-assisted morphometric (r2 = 0.84) estimates of hepatic steatosis from histological specimens.ConclusionsThis MRI approach, using a conventional, rapid, gradient echo method, has high sensitivity and specificity for diagnosing liver fat at all grades of steatosis in a cohort with a range of liver diseases.

Neuroimaging methods for adolescent substance use disorder prevention science.

Magnetic resonance imaging (MRI) methods safely provide in vivo indicators of cerebral macrostructure, microstructure, and activation that can be examined in relation to substance use disorder (SUD) risks and effects. This article will provide an overview of MRI approaches, including volumetric measures, diffusion tensor imaging, and functional MRI, that have been applied to studies of adolescent neuromaturation in relationship to risk phenotypes and adolescent SUD. To illustrate these applications, examples of research findings will be presented. MRI indicators have demonstrated that neurobiological maturation continues throughout adolescence. MRI research has suggested that variations in neurobiological maturation may contribute to SUD risk, and that substance use adversely influences adolescent brain development. Directly measured neurobiological variables may be viable preventive intervention targets and outcome indicators. Further research is needed to provide definitive findings on neurodevelopmental immaturity as an SUD risk and to determine the directions such observations suggest for advancing prevention science.

Decreased retinal–choroidal blood flow in retinitis pigmentosa as measured by MRI

To evaluate retinal and choroidal blood flow (BF) using high-resolution magnetic resonance imaging (MRI) as well as visual function measured by the electroretinogram (ERG) in patients with retinitis pigmentosa (RP). MRI studies were performed in 6 RP patients (29-67 years) and 5 healthy volunteers (29-64 years) on a 3-Tesla scanner with a custom-made surface coil. Quantitative BF was measured using the pseudo-continuous arterial spin-labeling technique at 0.5 × 0.8 × 6.0 mm. Full-field ERGs of all patients were recorded. Amplitudes and implicit times of standard ERGs were analyzed. Basal BF in the posterior retinal-choroid was 142 ± 16 ml/100ml/min (or 1.14 ± 0.13 μl/mm(2)/min) in the control group and was 70 ±19 ml/100ml/min (or 0.56 ± 0.15 μl/mm(2)/min) in the RP group. Retinal-choroidal BF was significantly reduced by 52 ± 8 % in RP patients compared to controls (P<0.05). ERG a- and b-wave amplitudes of RP patients were reduced, and b-wave implicit times were delayed. There were statistically significant correlations between a-wave amplitude and BF value (r=0.9, P<0.05) but not between b-wave amplitude and BF value (r =0.7, P=0.2). This study demonstrates a novel non-invasive MRI approach to measure quantitative retinal and choroidal BF in RP patients. We found that retinal-choroidal BF was markedly reduced and significantly correlated with reduced amplitudes of the a-wave of the standard combined ERG.

A Supervised Learning Approach for Crohn's Disease Detection Using Higher-Order Image Statistics and a Novel Shape Asymmetry Measure

Increasing incidence of Crohn's disease (CD) in the Western world has made its accurate diagnosis an important medical challenge. The current reference standard for diagnosis, colonoscopy, is time-consuming and invasive while magnetic resonance imaging (MRI) has emerged as the preferred noninvasive procedure over colonoscopy. Current MRI approaches assess rate of contrast enhancement and bowel wall thickness, and rely on extensive manual segmentation for accurate analysis. We propose a supervised learning method for the identification and localization of regions in abdominal magnetic resonance images that have been affected by CD. Low-level features like intensity and texture are used with shape asymmetry information to distinguish between diseased and normal regions. Particular emphasis is laid on a novel entropy-based shape asymmetry method and higher-order statistics like skewness and kurtosis. Multi-scale feature extraction renders the method robust. Experiments on real patient data show that our features achieve a high level of accuracy and perform better than two competing methods.

Noninvasive dualMRI-based strains vary by depth and region in human osteoarthritic articular cartilage

To noninvasively assay the mechanical and structural characteristics of articular cartilage from patients with osteoarthritis (OA) by magnetic resonance imaging (MRI), and to further relate spatial patterns of MRI-based mechanical strain to joint (depth-wise, regional) locations and disease severity. Cylindrical osteochondral explants harvested from human tissue obtained during total knee replacement surgery were loaded in unconfined compression and 2D deformation data was acquired at 14.1 T using a displacements under applied loading by MRI (dualMRI) approach. After imaging, samples were histologically assessed for OA severity. Strains were determined by depth, and statistically analyzed for dependence on region in the joint and OA severity. Von Mises, axial, and transverse strains were highly depth-dependent. After accounting for other factors, Von Mises, axial, and shear strains varied significantly by region, with largest strain magnitudes observed in explants harvested from the tibial plateau and anterior condyle near exposed bone. Additionally, in all cases, strains in late-stage OA were significantly greater than either early- or mid-stage OA. Transverse strain in mid-stage OA explants, measured near the articular surface, was significantly higher than early-stage OA explants. dualMRI was demonstrated in human OA tissue to quantify the effects of depth, joint region, and OA severity, on strains resulting from mechanical compression. These data suggest dualMRI may possess a wide range of utility, such as validating computational models of soft tissue deformation, assaying changes in cartilage function over time, and perhaps, once implemented for cartilage imaging in vivo, as a new paradigm for diagnosis of early- to mid-stage OA.

MRI/MRS evaluation of a female carrier of Duchenne muscular dystrophy

The purpose of this study was to evaluate skeletal muscle composition of lower extremity muscles in a manifesting female carrier of Duchenne muscular dystrophy (MFC(DMD)) using magnetic resonance imaging (MRI) and spectroscopy (MRS). MRI/MRS was performed on the lower extremities and heart of a MFC(DMD) (47 years, 51 kg) on four occasions within 21 months and in a control subject. Heterogeneity and asymmetry among muscles in the MFC(DMD) was observed in lipid fraction and mean transverse relaxation time (T(2)) of lower extremity muscles with some muscles presenting as unaffected (e.g., rectus femoris) and others showing substantial deterioration and lipid infiltration (e.g., vasti muscles). There was an association of abnormal MRI findings and strength and motor function. Over the 21 months a small decrease in CSA(max) and increase in lipid fraction and T(2) was observed in the MFC(DMD) in some muscles. In summary, this MFC(DMD) revealed significant imaging evidence of pathologic heterogeneity among muscles. Furthermore, this study shows the feasibility of combining various quantitative MRI and MRS approaches to monitor skeletal muscle involvement.

A Gated-7T MRI Technique for Tracking Lung Tumor Development and Progression in Mice after Exposure to Low Doses of Ionizing Radiation

A gated-7T magnetic resonance imaging (MRI) application is described that can accurately and efficiently measure the size of in vivo mouse lung tumors from ∼0.1 mm(3) to >4 mm(3). This MRI approach fills a void in radiation research because the technique can be used to noninvasively measure the growth rate of lung tumors in large numbers of mice that have been irradiated with low doses (<50 mGy) without the additional radiation exposure associated with planar X ray, CT or PET imaging. High quality, high resolution, reproducible images of the mouse thorax were obtained in ∼20 min using: (1) a Bruker 7T micro-MRI scanner equipped with a 60 mm inner diameter gradient insert capable of generating a maximum gradient of 1000 mT/m; (2) a 35 mm inner diameter quadrature radiofrequency volume coil; and (3) an electrocardiogram and respiratory gated Fast Low Angle Shot (FLASH) pulse sequence. The images had an in-plane image resolution of 98 μm and a 0.5 mm slice thickness. Tumor diameter measured by MRI was highly correlated (R(2) = 0.97) with the tumor diameter measured by electronic calipers. Data generated with an initiation/promotion mouse model of lung carcinogenesis and this MRI technique demonstrated that mice exposed to 4 weekly fractions of 10, 30 or 50 mGy of CT radiation had the same lung tumor growth rate as that measured in sham-irradiated mice. In summary, this high-field, double-gated MRI approach is an efficient way of quantitatively tracking lung tumor development and progression after exposure to low doses of ionizing radiation.

Neuroimaging in aphasia treatment research: Quantifying brain lesions after stroke

New structural and functional neuroimaging methods continue to rapidly develop, offering promising tools for cognitive neuroscientists. In the last 20 years, advanced magnetic resonance imaging (MRI) techniques have provided invaluable insights into how language is represented and processed in the brain and how it can be disrupted by damage to, or dysfunction of, various parts of the brain. Current functional MRI (fMRI) approaches have also allowed researchers to purposefully investigate how individuals recover language after stroke. This paper presents recommendations for quantification of brain lesions derived from discussions among international researchers at the Neuroimaging in Aphasia Treatment Research Workshop held at Northwestern University (Evanston, Illinois, USA). Methods for detailing and characterizing the brain damage that can influence results of fMRI studies in chronic aphasic stroke patients are discussed. Moreover, we aimed to provide the reader with a set of general practical guidelines and references to facilitate choosing adequate structural imaging strategies that facilitate fMRI studies in aphasia treatment research.

Measuring the interaction of meal and gastric secretion: a combined quantitative magnetic resonance imaging and pharmacokinetic modeling approach

The stimulation and intragastric accumulation of gastric secretion has been recognized as an important factor in gastroesophageal reflux disease. However, the interaction of gastric secretion and meal emptying has not been fully understood. Current methods to assess gastric secretion are either invasive or unable to provide information on its volume, distribution and dynamics. The aim of this study was to quantify the interaction between meal emptying and meal induced gastric secretion by using quantitative magnetic resonance imaging (MRI) and pharmacokinetic analysis. A chocolate test meal was developed which is secretion stimulating and MRI compatible. Meal emptying and gastric secretion were assessed in fourteen healthy volunteers using a validated quantitative MRI technique. A population based pharmacokinetic model was developed and applied to the extracted volume data, assessing the meal emptying rate, rate of secretion and their interaction. The test meal continuously induced gastric secretion in all subjects, which partly accumulated at the meal-air interface, forming a 'secretion layer' in the proximal stomach. Traditional fitting detected a significant correlation between meal emptying rate and rate of secretion. The pharmacokinetic model quantified this interaction and estimated a 2.3 ± 1 fold higher effect of meal on secretion than vice versa. The efficacy of the emptied meal to produce gastric secretion was 61%. The combined quantitative MRI and pharmacokinetic model approach allows for the quantification of gastric secretion volume and its interaction on meal emptying. The observed secretion layer might explain previous findings postulating the presence of an intragastric 'acid pocket'.