PubMed Health⌕ Search

Biomedical subjects

Joseph A Helpern

Publications and source records attributed to Joseph A Helpern.

15 recordsLinked to original sources
PubMed2006

Magnetic field correlation imaging.

A magnetic resonance imaging (MRI) method is presented for estimating the magnetic field correlation (MFC) associated with magnetic field inhomogeneities (MFIs) within biological tissues. The method utilizes asymmetric spin echoes and is based on a detailed theory for the effect of MFIs on nuclear magnetic resonance (NMR) signal decay. The validity of the method is supported with results from phantom experiments at 1.5 and 3 T, and human brain images obtained at 3 T are shown to demonstrate the method's feasibility. The preliminary results suggest that MFC imaging may be useful for the quantitative assessment of iron within the brain.

Algorithms↗
PubMed2006

Three-dimensional characterization of non-gaussian water diffusion in humans using diffusion kurtosis imaging.

Conventional diffusion tensor imaging (DTI) measures water diffusion parameters based on the assumption that the spin displacement distribution is a Gaussian function. However, water movement in biological tissue is often non-Gaussian and this non-Gaussian behavior may contain useful information related to tissue structure and pathophysiology. Here we propose an approach to directly measure the non-Gaussian property of water diffusion, characterized by a four-dimensional matrix referred to as the diffusion kurtosis tensor. This approach does not require the complete measurement of the displacement distribution function and, therefore, is more time efficient compared with the q-space imaging technique. A theoretical framework of the DK calculation is established, and experimental results are presented for humans obtained within a clinically feasible time of about 10 min. The resulting kurtosis maps are shown to be robust and reproducible. Directionally-averaged apparent kurtosis coefficients (AKC, a unitless parameter) are 0.74 +/- 0.03, 1.09 +/- 0.01 and 0.84 +/- 0.02 for gray matter, white matter and thalamus, respectively. The three-dimensional kurtosis angular plots show tissue-specific geometry for different brain regions and demonstrate the potential of identifying multiple fiber structures in a single voxel. Diffusion kurtosis imaging is a useful method to study non-Gaussian diffusion behavior and can provide complementary information to that of DTI.

Adult↗
PubMed2006

Quantitative MR imaging in Alzheimer disease.

Alzheimer disease (AD) is the most common type of dementia. It currently affects approximately 4 million people in the United States. AD is a progressive neurodegenerative disorder characterized by the gradual deposition of neuritic plaques and neurofibrillary tangles in the brain, which is thought to occur decades before the onset of clinical symptoms. Identification of people at risk before the clinical appearance of dementia has become a priority due to the potential benefits of therapeutic intervention. Although atrophy of medial temporal lobe structures has been shown to correlate with progression of AD, a growing number of recent reports have indicated that such atrophy may not be specific to AD. To improve diagnostic specificity, new quantitative magnetic resonance (MR) imaging methods are being developed that exploit known pathogenic mechanisms exclusive to AD. This article reviews the MR techniques that are currently available for the diagnostic assessment of AD.

Alzheimer Disease↗
PubMed2005

Diffusional kurtosis imaging: the quantification of non-gaussian water diffusion by means of magnetic resonance imaging.

A magnetic resonance imaging method is presented for quantifying the degree to which water diffusion in biologic tissues is non-Gaussian. Since tissue structure is responsible for the deviation of water diffusion from the Gaussian behavior typically observed in homogeneous solutions, this method provides a specific measure of tissue structure, such as cellular compartments and membranes. The method is an extension of conventional diffusion-weighted imaging that requires the use of somewhat higher b values and a modified image postprocessing procedure. In addition to the diffusion coefficient, the method provides an estimate for the excess kurtosis of the diffusion displacement probability distribution, which is a dimensionless metric of the departure from a Gaussian form. From the study of six healthy adult subjects, the excess diffusional kurtosis is found to be significantly higher in white matter than in gray matter, reflecting the structural differences between these two types of cerebral tissues. Diffusional kurtosis imaging is related to q-space imaging methods, but is less demanding in terms of imaging time, hardware requirements, and postprocessing effort. It may be useful for assessing tissue structure abnormalities associated with a variety of neuropathologies.

Anisotropy↗
PubMed2005

Novel approach to the measurement of absolute cerebral blood volume using vascular-space-occupancy magnetic resonance imaging.

Quantitative determination of cerebral blood volume (CBV) is important for understanding brain physiology and pathophysiology. In this work, a novel approach is presented for accurate measurement of absolute CBV (aCBV) using vascular-space-occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T(1) shortening property of Gd-DTPA. Two VASO images with identical imaging parameters are acquired before and after contrast agent injection, resulting in a subtracted image that reflects the amount of blood present in the brain, i.e., CBV. With an additional normalizing factor, aCBV in units of milliliters of blood per 100 mL of brain can be estimated. Experimental results at 1.5 and 3 T systems showed that aCBV maps with high spatial resolution can be obtained with high reproducibility. The averaged aCBV values in gray and white matter were 5.5 +/- 0.2 and 1.4 +/- 0.1 mL of blood/100 mL of brain, respectively. Compared to dynamic susceptibility contrast techniques, VASO MRI is based upon a relatively straightforward theory and the calculation of CBV does not require measurement of an arterial input function. In comparison with previous pre/postcontrast difference approaches, VASO MRI provides maximal signal difference between pre- and postcontrast situation and does not require the use of whole blood for signal normalization.

Adult↗
PubMed2005

Histological co-localization of iron in Abeta plaques of PS/APP transgenic mice.

This study confirms the presence of iron, co-localized with Abeta plaques, in PS/APP mouse brain, using Perls' stain for Fe3+ supplemented by 3,3'-diaminobenzidine (DAB) and Abeta immunohistochemistry in histological brains sections fixed with formalin or methacarn. In this study, the fixation process and the slice thickness did not interfere with the Perls' technique. The presence of iron in beta-amyloid plaques in PS/APP transgenic mice, a model of Alzheimer's disease (AD) pathology, may explain previous reports of reductions of transverse relaxation time (T2) in MRI studies and represent the source of the intrinsic Abeta plaque MR contrast in this model.

3,3'-Diaminobenzidine↗
PubMed2004

MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease.

The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD.

Alzheimer Disease↗
PubMed2004

Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents.

The visualization of beta-amyloid plaque deposition in brain, a key feature of Alzheimer's disease (AD), is important for the evaluation of disease progression and the efficacy of therapeutic interventions. In this study, beta-amyloid plaques in the PS/APP transgenic mouse brain, a model of human AD pathology, were detected using MR microscopy without contrast reagents. beta-Amyloid plaques were clearly visible in the cortex, thalamus, and hippocampus of fixed brains of PS/APP mice. The distribution of plaques identified by MRI was in excellent agreement with those found in the immunohistological analysis of the same brain sections. It was also demonstrated that image contrast for beta-amyloid plaques was present in freshly excised nonfixed brains. Furthermore, the detection of beta-amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging.

Alzheimer Disease↗
PubMed2004

Quantitative MRI assessment of Alzheimer's disease.

The development of a noninvasive method to detect early, subtle changes in the brains of patients with Alzheimer's disease (AD) would have considerable clinical value as therapy. This therapy is most likely to be successful if intervention could occur before neurons were irreversibly damaged or lost. An ideal biological neuroimaging marker would be an early, sensitive, and valid indicator of brain changes, capable of discriminating the effects of normal aging. The introduction of high field-strength clinical magnetic resonance imaging (MRI) systems now offer a powerful new noninvasive tool that may be capable of detecting brain pathology resulting from AD. Here we present results from high field-strength MRI in transgenic mice along with a new MRI technique for imaging brain iron. The successful translation of this research to the clinic could prove important to both the early diagnosis and monitoring of the efficacy of potential therapies in humans.

Alzheimer Disease↗
PubMed2003

Quantitative measurements of proton spin-lattice (T1) and spin-spin (T2) relaxation times in the mouse brain at 7.0 T.

The goal of this work is to provide regional T(1) and T(2) values at a field strength of 7 T for the normal mouse brain at 6 weeks and 1 year old. A novel segmented snapshot FLASH sequence was used to measure T(1) in the hippocampus, corpus callosum, and the retrosplenial granular (RSG) cortex; T(2) measurements were made in the same regions using a single spin echo sequence repeated at six separate echo times. Both T(1) and T(2) measurements were validated with phantom measurements.

Age Factors↗
PubMed2003

Diffusion tensor imaging in fixed brain tissue at 7.0 T.

The purpose of this work is to assess the feasibility of performing quantitative in vitro brain tissue diffusion tensor imaging (DTI) measurements and to examine their comparability to in vivo measurements. DTI of fixed tissue at high field strength is potentially a very valuable investigative tool as very high spatial resolution can be achieved. DTI was applied to human and mouse brain fixed tissue samples as well as in vivo measurements of the mouse brain. T(1) and T(2) relaxography of the fixed tissue samples was also performed to provide further characterization of the tissue. All experiments were performed at 7 T. The fractional anisotropy (FA) of the human fixed brain tissue samples is found to be higher in the corpus callosum than in the occipital white matter region, consistent with in vivo measurements reported in the literature. Our FA measurements of the corpus callosum of a mouse brain are also found to be the same both in vitro and in vivo. This preliminary work supports the use of DTI in both fixed human and fixed animal brain tissue as a valid investigative tool. With the increased availability of brain banks in different brain disorders, DTI in fixed tissue may prove to be a very useful method for the study of white matter abnormalities.

Animals↗
PubMed2003

In vivo NMR studies of neurodegenerative diseases in transgenic and rodent models.

In vivo magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide unique quality to attain neurochemical, physiological, anatomical, and functional information non-invasively. These techniques have been increasingly applied to biomedical research and clinical usage in diagnosis and prognosis of diseases. The ability of MRS to detect early yet subtle changes of neurochemicals in vivo permits the use of this technology for the study of cerebral metabolism in physiological and pathological conditions. Recent advances in MR technology have further extended its use to assess the etiology and progression of neurodegeneration. This review focuses on the current technical advances and the applications of MRS and MRI in the study of neurodegenerative disease animal models including amyotrophic lateral sclerosis, Alzheimer's, Huntington's, and Parkinson's diseases. Enhanced MR measurable neurochemical parameters in vivo are described in regard to their importance in neurodegenerative disorders and their investigation into the metabolic alterations accompanying the pathogenesis of neurodegeneration.

Animals↗
PubMed2002

Functional magnetic resonance imaging of brain activity in the visual oddball task.

Abnormalities in the P300 ERP, elicited by the oddball task and measured using EEG, have been found in a number of central nervous system disorders including schizophrenia, Alzheimer's disease, and alcohol dependence. While electrophysiological studies provide high temporal resolution, localizing the P300 deficit has been particularly difficult because the measurements are collected from the scalp. Knowing which brain regions are involved in this process would elucidate the behavioral correlates of P300. The aim of this study was to determine the brain regions involved in a visual oddball task using fMRI. In this study, functional and high-resolution anatomical MR images were collected from seven normal volunteers. The data were analyzed using a randomization-based statistical method that accounts for multiple comparisons, requires no assumptions about the noise structure of the data, and does not require spatial or temporal smoothing. Activations were detected (P<0.01) bilaterally in the supramarginal gyrus (SMG; BA 40), superior parietal lobule (BA 7), the posterior cingulate gyrus, thalamus, inferior occipitotemporal cortex (BA 19/37), insula, dorsolateral prefrontal cortex (BA 9), anterior cingulate cortex (ACC), medial frontal gyrus (BA 6), premotor area, and cuneus (BA 17). Our results are consistent with previous studies that have observed activation in ACC and SMG. Activation of thalamus, insula, and the occipitotemporal cortex has been reported less consistently. The present study lends further support to the involvement of these structures in visual target detection.

Adult↗