Biomedical subjects

J A Helpern

Publications and source records attributed to J A Helpern.

At least 19 recordsLinked to original sources

PubMed1999

Rapid and continuous monitoring of cerebral perfusion by magnetic resonance line scan assessment with arterial spin tagging.

A new approach is presented for rapid and continuous monitoring of cerebral perfusion which is based upon line-scan MR column imaging with arterial spin tagging (AST) of endogenous water. Spin tagging of arterial water protons is accomplished using adiabatic fast passage inversion, followed by acquisition of the perfusion sensitive MR signal from a column placed at the desired level through the brain using line scan localization techniques. A perfusion sensitive line scan is followed by a non-perfusion sensitive line scan, and perfusion is calculated pixel-by-pixel from the intensity difference of the two lines. Continuous perfusion measurements are reported with temporal resolution of 10 s in pixels of volume 0.027 cm3 or less. Examples of the methodology are given during hypercapnic challenge induced with carbon dioxide, and during an ischemic event induced by reversible middle cerebral artery occlusion. The method is also used to characterize the signal response as a function of arterial inversion time and post inversion acquisition delay. These methods permit rapid and continuous monitoring of cerebral perfusion with high spatial resolution, and can be interleaved with MR measurements of diffusion and T1 to follow the progression of cerebral events during physiological or pharmacological intervention.

Animals↗

PubMed1999

MR perfusion imaging in human brain using the UNFAIR technique. Un-inverted flow-sensitive alternating inversion recovery.

Pulsed arterial spin labeling magnetic resonance techniques have been developed recently to estimate cerebral blood flow (CBF). Flow-sensitive alternating inversion recovery (FAIR) is one such technique that has been implemented successfully in humans. Un-inverted FAIR (UNFAIR) is an alternative technique in which the flow-sensitive image is acquired following inversion of all spins outside the slice of interest, and the control image is acquired without any spin labeling. This approach is potentially more efficient than FAIR since the UNFAIR control image is entirely flow independent and need only be acquired once. Here, we describe implementation of the sequence on a clinical 1.5 T magnetic resonance system. Both FAIR and UNFAIR perfusion-weighted images were obtained from six normal volunteers. Wash-in/wash-out curves measured in cortical gray and white matter were practically identical for the two techniques, as predicted by our model.

Adult↗

PubMed1998

The influence of preischemic hyperglycemia on acute changes in brain water ADCw following focal ischemia in rats.

The effect of preischemic hyperglycemia on the acute decline of brain apparent diffusion coefficient of water (ADCw) following cerebral ischemia was studied in a rat model of middle cerebral artery occlusion (MCAO). ADCw was measured by NMR with a newly developed spin-echo line-scan protocol that provides for an ADCw calculation every 15 s at a spatial resolution of 3.4 microl/pixel. A remote controlled occluding device was used to initiate ischemia from outside the magnet, allowing for continuous monitoring of ADCw before, during and after MCAO. Preischemic hyperglycemia (25-30 mM) was achieved via i.v. infusion of 50% glucose. The decline in ADCw following ischemia was analyzed to obtain three-time constants: the time from onset of ischemia to initial significant ADCw decline below baseline level (i.e., 20% of maximal decline, T0.20), the time to decline by 50% (T0.50), and the time to decline by 95% (T0.95). Mean (+/-S.D.) values for T0.20, T0.50, T0.95 were: 39.6+/-7.2, 54. 0+/-7.8, 105.0+/-15.0 s for the normoglycemic group (n=7), and 49. 2+/-33.0, 116.4+/-2.4, 351.0+/-189.0 s for the hyperglycemic group (n=6), respectively. Hyperglycemia significantly prolongs T0.50 and T0.95 but does not affect T0.20. The temporal profiles of ADCw decline following ischemia under normo- and hyperglycemia are distinctively different from the known time course of membrane depolarization under similar experimental conditions, suggesting that mechanisms other than membrane depolarization and cell swelling may contribute to changes in ADCw in cerebral ischemia.

Animals↗

PubMed1998

Perfusion imaging using FOCI RF pulses.

Pulsed arterial spin-tagging techniques for perfusion measurements (e.g., echo planar MR imaging and signal targeting with alternating radiofrequency (EPISTAR), flow-sensitive alternating inversion recovery (FAIR), quantitative imaging of perfusion using a single subtraction (QUIPPS), uninverted FAIR (UNFAIR)) generally use hyperbolic secant (HS) pulses for spin inversion. The performance of these techniques depends on the inversion efficiency, as well as the sharpness of the slice profiles. Frequency offset corrected inversion (FOCI) pulses, a recently proposed HS variant, can provide slice profiles with edges that can be up to 10 times sharper than those obtained with conventional HS pulses. In this communication, the implementation and application of the C-shape FOCI pulse for perfusion imaging in rat brain with the FAIR technique is summarized. Despite providing a more rectangular slice profile than a conventional HS pulse, it is demonstrated both theoretically and experimentally that the FAIR perfusion signal is not increased by using a FOCI tagging pulse. However, the use of a FOCI inversion pulse is shown to significantly minimize static signal subtraction errors that are common with conventional HS pulses. Finally, the suitability of the pulse for perfusion studies is demonstrated, in vivo, on rat brain.

Animals↗

PubMed1997

The influence of preischemic hyperglycemia on acute changes in the apparent diffusion coefficient of brain water following global ischemia in rats.

We report the effect of increased plasma glucose levels on changes in the apparent diffusion coefficient of brain water (ADCw) during the first few minutes of global ischemia in rats. Brain ADCw values were acquired every 15 s using a diffusion-weighted line-scan MR pulse sequence. Preischemic hyperglycemia was achieved by infusion of 50% dextrose (i.v.) prior to KCl-induced cardiac arrest global ischemia. Analysis based on single voxels (3.4 microl) in brain demonstrated significant differences in the time course of ADCw decline between normoglycemic (n = 8) and hyperglycemic (n = 6) groups. Mean data from the hyperglycemic group indicated a biphasic decline of ADCw that was characterized by an initial rapid drop followed by a plateau of approximately 1 min before gradually declining and leveling off to its minimum value. In the normoglycemic group, ADCw declined to the same value as in the hyperglycemic group, but without a notable plateau. In the cerebral cortex, the times to maximal and half maximal ADCw drop following global ischemia in the hyperglycemic group were 3.96 and 2.26 min respectively. Corresponding time intervals for the normoglycemic group were 1.86 and 1.14 min, respectively. The time course for changes in ADCw demonstrated here is significantly different than that for anoxic depolarization reported under similar experimental conditions and suggests that events other than the complete loss of membrane ionic homeostasis and subsequent cell swelling may be involved in the initial decline of ADCw in global cerebral ischemia.

Animals↗

PubMed1997

The application of diffusion-weighted line-scanning for the rapid assessment of water ADC changes in stroke at high magnetic fields.

Rapid changes in the apparent diffusion coefficient of water following brain ischemia have been extensively studied using echo planar diffusion imaging at low fields (2.0 T). There is a desire to perform these studies at higher fields (> 3.0 T) where the benefits of improved signal-to-noise can be exploited. Unfortunately, EPI diffusion is technically difficult to implement at high fields because of large magnetic susceptibility effects. This article demonstrates the feasibility of employing a line-scan diffusion protocol for ADCw measurements in stroke. The technique was applied on a 4.0 T system to monitor the decline in ADCw following the induction of focal cerebral ischemia in rat. ADCw data were acquired every 15 s with 10 b-values or every 22.5 s with 15 b-values, with a cubic spatial resolution of 1.5 mm. The results demonstrate that estimates of ADCw can be acquired with coefficients of variation under 3.0%, and with a combination of spatial and temporal resolution comparable to that previously reported for EPI.

Animals↗

PubMed1997

Perfusion imaging by un-inverted flow-sensitive alternating inversion recovery (UNFAIR).

A new pulse sequence for estimating cerebral blood flow called UNFAIR, which uses a combination of sequential hyperbolic secant preparatory pulses, is introduced. This sequence is based on the same generalized conditions as previously introduced inversion recovery techniques except that the spins in the image slice of interest always have +z magnetization and the in-flowing spins are alternately inverted and uninverted. CBF-weighted images of rat brain under conditions of normocpnia and hypercapnia are presented and demonstrate the expected CBF response. A model describing the signal response to this pulse sequence is also presented and compared with in-vivo data acquired from gray and white matter.

Animals↗

PubMed1995

Abnormalities of skeletal muscle metabolism during nerve stimulation determined by 31P nuclear magnetic resonance spectroscopy in severe congestive heart failure.

These data confirm the presence of abnormal skeletal muscle metabolic function in patients with chronic heart failure. These changes are independent of patient compliance and central hemodynamic response to conventional exercise, and may explain, in part, the marked decrease in exercise tolerance often observed in patients with chronic severe heart failure. The etiology of these abnormalities of metabolic function and nutritive flow remains uncertain. TNS may prove useful in further elucidation of the peripheral metabolic consequences of chronic heart failure.

Acute Disease↗

PubMed1995

Preliminary observations of transverse relaxation rates obtained at 3 tesla from the substantia nigra of adult normal human brain.

The transverse relaxation rates R2 and R2* were measured at 3 T in the substantia nigra of the midbrain of adult normal human controls. The relaxation rate arising from magnetic inhomogeneities, R2', was calculated from the relationship R2* = R2 + R2'. No significant differences were found for any parameters between left and right side substantia nigra regions, however, a significant inverse correlation was found between R2 and R2' (r = 0.70, p = 0.035). Water diffusion, in the presence of paramagnetic metal ions, may play a role in determining the relative contributions to reversible and irreversible transverse relaxation and may explain the inverse correlation demonstrated here.

Aged↗

PubMed1995

Diffusion-weighted imaging in epilepsy.

Diffusion-weighted imaging (DWI) is a relatively new magnetic resonance imaging (MRI) technique that can be used to probe the microenvironment of water. Contrast in DWI depends on properties different from traditional T1 and T2 contrast, and is derived form the translational motion of water molecules. Since it is reasonable to think that a change in the microenvironment of water might be reflected in a change in water diffusion characteristics, the quantitative assessment of the (apparent) diffusion coefficient ADCw may represent a unique means of assessing tissue status. DWI has already shown great utility in the study of cerebral ischemia in animal models and has proved useful in the early identification of cerebral ischemia in patients. More recent reports have indicated a potential for DWI in studying epilepsy. Here, we briefly review some of what is known about the measurement of ADCw in ischemia and compare these results with what has recently been reported for epilepsy. In this manner we hope to better understand the underlying mechanisms behind changes in water diffusion associated with specific pathologies.

Animals↗

PubMed1995

Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease.

Elevated iron levels in the substantia nigra (SN) of the brain in Parkinson's disease (PD) may mediate lipid peroxidative reactions, promoting SN neuronal death. To assess SN iron accumulation in living PD patients and its relation to motor performance, we measured, in 13 nondemented PD patients and 10 normal control subjects, simple reaction time (SRT) and simple movement time (SMT), followed by head MRI in a 3-tesla system. We measured T2 and T2* in the right and left SN of all subjects and calculated R2', the relaxation rate due to local magnetic field in-homogeneities, from these values. Asymmetries of 1/T2 (R2), 1/T2* (R2*), or R2' versus asymmetries of SRT and SMT were assessed in eight PD subjects who had not taken anti-PD medication(s) for 12 hours. The average of right and left SN values for R2 was lower, and R2* and R2' were higher, in PD patients than in controls (R2, p = 0.046; R2*, p = 0.001; R2', p < 0.001). R2' best predicted group differences. The asymmetry of SRT performance was highly correlated with asymmetries of SN R2* (0.91; p = 0.001) and R2' (0.72; p = 0.03). These results strongly suggest that the increases in iron levels seen postmortem in the SN in PD are reflected in increased iron-related MRI contrast at 3 tesla in living PD patients. Correlations with motor performance in PD suggest that the clinical severity of PD may be related to SN iron accumulation.

Adult↗

PubMed1994

Assessment of relative brain iron concentrations using T2-weighted and T2*-weighted MRI at 3 Tesla.

In this paper a new method is presented for the relative assessment of brain iron concentrations based on the evaluation of T2 and T2*-weighted images. A multiecho sequence is employed for rapid measurement of T2 and T2*, enabling calculation of the line broadening effect (T2'). Several groups have failed to show a correlation between T2 and brain iron content. However, quantification of T2', and the associated relaxation rate R2', may provide a more specific relative measure of brain iron concentration. This may find application in the study of brain diseases, which cause associated changes in brain iron levels. A new method of field inhomogeneity correction is presented that allows the separation of global and local field inhomogeneities, leading to more accurate T2* measurements and hence, T2' values. The combination of T2*, and T2-weighted MRI methods enables the differentiation of Parkinson's disease patients from normal age-matched controls based on differences in iron content within the substantia nigra.

Aged↗

PubMed1994

A low flip angle spin-echo technique for producing rapid diffusion weighted MR images.

A method is described for producing rapid diffusion-weighted images using a modified low flip angle imaging technique. Utility of the method is demonstrated by the quantification of diffusion coefficients in a rat model of focal ischemia. The method may be readily applied to animal research studies using NMR research systems with modest gradient capabilities.

Animals↗

PubMed1994

Correction of motional artifacts in diffusion-weighted MR images using navigator echoes.

Patient motion can seriously degrade the quality of diffusion-weighted MR images obtained using standard 2DFT imaging procedures. The main source of error arises from an MR signal phase-shift error which is proportional to the magnitude of the motion. A modified pulse sequence is proposed which uses the phase information from an additional spin echo to correct for patient motion. Application of this technique is demonstrated for a human brain study, which greatly improves the quantification of diffusion values from regions of brain tissue.

Artifacts↗

PubMed1994

The effect of hypothermia on transient focal ischemia in rat brain evaluated by diffusion- and perfusion-weighted NMR imaging.

The effect of moderate whole-body hypothermia (30 degrees C) on transient middle cerebral artery (MCA) occlusion in the rat was evaluated using diffusion- and perfusion-weighted magnetic resonance imaging. Two hours of transient MCA occlusion was induced by intracarotid insertion of a nylon filament under normothermic (n = 14) and hypothermic (n = 7) conditions. Diffusion- and perfusion-weighted imaging were performed before, during, and after focal ischemia from 30 min up to 7 days. In hypothermic animals, scattered neuronal necrosis was localized to select areas of the caudate putamen and the parietal and insular cortex. In contrast, the normothermic ischemic animals exhibited pan-necrosis and infarct encompassing the damaged area. The diffusion and perfusion data measured from caudate putamen indicate that hypothermia causes a significant reduction in the apparent diffusion coefficient of water (ADCw) and CBF values from normothermic control values (p < 0.01). In both normothermic and hypothermic animals after onset of MCA occlusion, ADCw and CBF values in the core of the ischemic region (striatum) significantly declined from the preischemic and homologous contralateral control ADCw and CBF values (p < 0.05). However, ADCw and CBF in the hypothermic group returned toward control more rapidly than in the normothermic group. These results suggest that the protective effect of hypothermia on ischemic cell damage is reflected in the early return of ADCw during reperfusion and the reduction of ischemic cell damage by hypothermia may be mediated by the improved CBF during acute reperfusion.

Animals↗

PubMed1994

Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats.

BACKGROUND AND PURPOSE: This study was performed to document the progression of ischemic brain damage after middle cerebral artery occlusion in the rat using magnetic resonance imaging and histopathologic methods. METHODS: Cerebral ischemia was induced through permanent tandem occlusion of ipsilateral middle cerebral and common carotid arteries. The evolution of magnetic resonance imaging and histopathologic parameter changes was studied, both short term (1.5 to 8 hours) and long term (24 to 168 hours), in five specific brain regions within the middle cerebral artery territory. RESULTS: Significant changes in proton nuclear magnetic resonance spin-lattice and spin-spin relaxation times and the "apparent" diffusion coefficient of water could be detected within hours after the onset of permanent focal cerebral ischemia, whereas significant alterations in proton spin-density ratios were not apparent until approximately 48 hours. Histological changes were evident within 12 hours, with a significant loss of neurons seen in the most severely damaged regions at 7 days. Diffusion-weighted imaging was the most sensitive technique for visualizing acute ischemic alterations. The water diffusion coefficient was the only magnetic resonance imaging parameter studied to indicate significant alterations within the first 4 hours after arterial occlusion in all five brain regions. CONCLUSIONS: The degree of change for a particular magnetic resonance imaging parameter appeared to be related to the location and extent of neuronal injury, with the most dramatic changes occurring within the areas displaying the most severe histological damage. These results indicate that complete specification of all brain regions affected by ischemic brain injury may require a combination of imaging strategies applied over a period of days and suggest the possibility of using magnetic resonance imaging to distinguish between permanent and reversible cell damage.

Animals↗

PubMed1993

Temporal evolution and spatial distribution of the diffusion constant of water in rat brain after transient middle cerebral artery occlusion.

The regional distribution and temporal evolution of the diffusion coefficient (Dw) of water in rat brain was measured during and after transient middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 14) were subjected to 2 h of middle cerebral artery occlusion, induced by intracarotid insertion of a filament. Diffusion (n = 14) and perfusion (n = 7) weighted magnetic resonance imaging were performed before, and at various time points after MCA occlusion, ranging from 30 min up to 7 days. Our data demonstrate that the temporal profiles of Dw differ between the severely and the least damaged regions of tissue. In the core of the lesion, where the tissue evolved to necrosis, Dw declined significantly (P < 0.001) within 0.5 h after onset of ischemia, and remained depressed until 24 h after withdrawal of the suture. However, no statistically significant decline in Dw was found in the perifocal regions containing morphologically intact cells. Perfusion MRI qualitatively exhibited a hypoperfusion and reperfusion during, and after 2 h MCA occlusion, respectively. A significant (r > or = 0.71, P < 0.01) correlation was found between delta Dw (the difference in Dw between the ipsilateral ischemic and homologous contralateral control regions) obtained immediately before withdrawal of the suture (2 h of ischemia) and at specific early time points after withdrawal of the suture, and the degree of ischemic cell damage. No significant (P > 0.01) correlation was detected at an early time points of ischemia or at other time points after withdrawal of the suture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Altered brain energy metabolism in demented patients with multiple subcortical ischemic lesions. Working hypotheses.

We report the results of brain metabolic studies (using magnetic resonance spectroscopy) in three groups of individuals: (1) demented patients with multiple subcortical ischemic lesions (n = 18); (2) nondemented, age-matched controls (n = 21); and (3) demented patients with neurodegenerative disease, probably of the Alzheimer type (n = 19). Patients with dementia with subcortical vascular lesions, as demonstrated by appropriate imaging studies, had an increase of phosphate energy charge in areas of the cerebral cortex (especially prominent in the frontal regions) superficial to and excluded from the subcortical lesions. We hypothesize that this increased energy charge might be caused by reduced metabolic activity of disconnected brain tissue or by astrocytic hypertrophy and hyperplasia that accompanies subtle ischemic, cortical alterations.

Adenosine Triphosphate↗