Biomedical subjects

P A Narayana

Publications and source records attributed to P A Narayana.

At least 19 recordsLinked to original sources

PubMed2007

High-resolution vascular imaging of the rat spine using liposomal blood pool MR agent.

BACKGROUND AND PURPOSE: High-resolution, vascular MR imaging of the spine region in small animals poses several challenges. The small anatomic features, extravascular diffusion, and low signal-to-noise ratio limit the use of conventional contrast agents. We hypothesize that a long-circulating, intravascular liposomal-encapsulated MR contrast agent (liposomal-Gd) would facilitate visualization of small anatomic features of the perispinal vasculature not visible with conventional contrast agent (gadolinium-diethylene-triaminepentaacetic acid [Gd-DTPA]). METHODS: In this study, high-resolution MR angiography of the spine region was performed in a rat model using a liposomal-Gd, which is known to remain within the blood pool for an extended period. The imaging characteristics of this agent were compared with those of a conventional contrast agent, Gd-DTPA. RESULTS: The liposomal-Gd enabled acquisition of high quality angiograms with high signal-to-noise ratio. Several important vascular features, such as radicular arteries, posterior spinal vein, and epidural venous plexus were visualized in the angiograms obtained with the liposomal agent. The MR angiograms obtained with conventional Gd-DTPA did not demonstrate these vessels clearly because of marked extravascular soft-tissue enhancement that obscured the vasculature. CONCLUSIONS: This study demonstrates the potential benefit of long-circulating liposomal-Gd as a MR contrast agent for high-resolution vascular imaging applications.

Animals↗

PubMed2006

Diffusion tensor imaging in polymicrogyria: a report of three cases.

INTRODUCTION: Polymicrogyria (PMG), a neuronal migration disorder, commonly manifests as a seizure disorder. The aim of this study was to look for the abnormalities in the underlying white matter using diffusion tensor imaging (DTI) that appeared normal on conventional magnetic resonance imaging (MRI) in patients with PMG. METHODS: DTI was performed in three patients with PMG and eight age- and sex-matched healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated for the cortex and adjoining subcortical white matter in both controls and patients. RESULTS: We observed a significantly decreased mean FA value with no significant change in the MD value in subcortical white matter underlying polymicrogyric cortex (FA = 0.23+/-0.04, MD = 1.0+/-0.05 x 10(-3) mm(2)/s) as compared to both contralateral (FA = 0.32+/-0.04, MD = 1.0+/-0.05 x 10(-3) mm(2)/s) and normal control (FA = 0.32+/-0.04, MD = 1.0+/-0.06 x 10(-3) mm(2)/s) white matter. Significantly increased MD and decreased FA values were also observed in the polymicrogyric cortex (FA = 0.08+/-0.01, MD = 1.2+/-0.10 x 10(-3) mm(2)/s) as compared to normal contralateral (FA = 0.12+/-0.04, MD = 1.1+/-0.09 x 10(-3) mm(2)/s) and normal control (FA = 0.12+/-0.01, MD = 1.1+/-0.09 x 10(-3) mm(2)/s) cortex. CONCLUSION: Significantly decreased FA values with no change in MD values in the subcortical white matter subjacent to polymicrogyric cortex reflect microstructural changes in the white matter probably due to the presence of ectopic neurons.

Adult↗

PubMed2006

Assessment of white matter damage in subacute sclerosing panencephalitis using quantitative diffusion tensor MR imaging.

BACKGROUND AND PURPOSE: Subacute sclerosing panencephalitis (SSPE), a rare progressive degenerative disease, is caused by persistent infection with a defective measles virus. The correlation between the clinical staging and MR imaging is usually poor. The aim of the study was to investigate the role of diffusion tensor imaging (DTI) in the early detection of white matter damage in SSPE in the presence of normal findings on conventional imaging. METHODS: DTI was performed in 21 patients in stage II SSPE and 10 age/sex-matched healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in the periventricular white matter, corpus callosum, and posterior limb of the internal capsule in patients with normal and abnormal findings on conventional imaging as well as healthy controls. RESULTS: The patients were grouped into those with normal (n = 11) and abnormal (n = 10) findings on conventional imaging for the purpose of quantitative DTI analysis. Abnormal- and normal-appearing white matter on T2-weighted images showed significantly decreased FA values in all the regions compared with those in healthy controls. MD values were significantly increased in the periventricular white matter region of the frontal and parietooccipital lobe in patients with normal as well as abnormal findings on conventional imaging compared with those in healthy controls. CONCLUSION: DTI detects early white matter abnormalities that may have significant therapeutic implication, even in the presence of normal findings on conventional imaging, in patients with SSPE.

Adolescent↗

PubMed2005

Pilot study to examine the effect of antibiotic therapy on MRI outcomes in RRMS.

This trial examined the safety and possible MRI and clinical effects of anti-chlamydial antibiotic therapy in relapsing-remitting MS (RRMS). Newly diagnosed MS patients were selected to participate if they showed Chlamydia pneumoniae gene in their CSF and had one or more enhancing lesions on brain magnetic resonance imaging (MRI). After a 4-month run in phase of monthly MRI, patients were randomized to receive rifampin (300 mg twice daily) and azithromycin (500 mg every other day) for 6 months or placebo (PBO). Patients then had monthly MRI on therapy and two additional scans on months 12 and 14. Lumbar punctures were repeated between months 7 and 8 and within 2 weeks of termination of the study. Data on 4 patients on treatment and 4 on PBO were available for analysis. The primary outcome measure of showing a beneficial effect on enhancing lesions was not met. However, there was a significant difference in brain parenchymal fraction loss favoring those patient receiving antibiotics compared with PBO (p< or =0.02). Three of the four patients on antibiotic therapy cleared the organism from the CSF by month 12; in the PBO group one patient cleared the organism. The reduction in atrophy in patients receiving antibiotics must be viewed with caution, due to the small number of patients studied.

Adult↗

PubMed2001

Ingested IFN-alpha: results of a pilot study in relapsing-remitting MS.

OBJECTIVE: To investigate whether ingested human recombinant interferon-alpha2a (IFN-alpha2a) was safe and whether treatment reduces the number of gadolinium-enhanced lesions on serial MRI in patients with active relapsing-remitting MS (RRMS). METHODS: Entry criteria included clinically definite RRMS and one or more gadolinium-enhanced lesions on a screening MRI. RESULTS: Of 80 patients screened, 33 were eligible and 30 patients were enrolled for treatment. Patients were randomized (10 per group) to placebo, 10,000 or 30,000 IU IFN-alpha2a ingested on alternate days for 9 months. They were examined clinically and with monthly cerebral MRI. Sample size projections were based on the assumption of a parenteral IFN-like effect, a 90% reduction of enhancing lesions evident within 1 month of the initiation of treatment in the active treatment groups sustained during the 9-month study as the primary outcome variable. RESULTS: There was no significant effect on enhancing lesions. However, post hoc analysis suggested a possible treatment effect in the 10,000 IU group. By direct monthly comparison of placebo and 10,000 IU group in treatment month 5, there were 73% (p < 0.05) fewer enhancements in the 10,000 IU group than in the placebo group. There was a decrease of tumor necrosis factor-alpha protein secretion at months 4 and 5. Relapses and adverse events were not different among the treatment groups. Ingested IFN-alpha2a did not induce systemic anti-IFN-alpha antibodies. CONCLUSIONS: This trial showed no benefit based on the primary outcome measure. Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect, IFN-alpha may deserve further study.

Administration, Oral↗

PubMed2001

Relationship of urinary myelin basic protein-like material with cranial magnetic resonance imaging in advanced multiple sclerosis.

BACKGROUND: A significant correlation exists between disability and the volume of black holes (BHL VOL), defined as hypointense lesions on T1-weighted cranial magnetic resonance imaging. A consistent correlation has also been reported between urinary myelin basic protein-like material (MBPLM) and the transition toward secondary progression (SP) from relapsing-remitting (RR) multiple sclerosis (MS). OBJECTIVE: To improve the management of MS through a noninvasive and cost-effective test for monitoring disease activity or disease status. DESIGN AND METHODS: From 662 patients with MS (86 with RR MS, 259 with SP MS without continued attacks, and 317 with SP MS with continued attacks), 24-hour urine samples were obtained at enrollment in the phase 3 Linomide (roquinimex) drug study. The urine specimens were analyzed for MBPLM and correlated with clinical features and findings on cranial magnetic resonance imaging. RESULTS: Significant but weak correlations existed between urinary MBPLM and BHL VOL in all patients with MS (r = 0.114, P =.003; n = 662), patients with SP MS without attacks (r = 0.185, P =.003; n = 259), and all patients with SP MS (r = 0.122, P =.003; n = 576). No significant correlations were detected in the RR MS group or any of the disease groups or subgroups whose Expanded Disability Status Scale score was 5.0 or lower. In subgroup analysis, the most significant correlation was detected between urinary MBPLM after adjustment for creatinine and BHL VOL in patients with SP MS with an Expanded Disability Status Scale score of 5.5 or higher but without continued relapses (r = 0.417, P<.001; n = 138). CONCLUSIONS: In patients with advanced SP MS, urinary MBPLM may possibly serve as an indicator of failed remission and axonal damage. Urinary MBPLM correlates with disease status in MS, especially the transition of RR MS to SP MS with advancing disability.

Adjuvants, Immunologic↗

PubMed2001

Dynamic contrast-enhanced MRI of experimental spinal cord injury: in vivo serial studies.

The progression of experimental spinal cord injury (SCI) was followed with in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and neurobehavioral studies on postinjury days 0, 2, 4, 7, 10, 14, 17, 21, 28, 35, and 42. Gadopentate dimeglumine (Gd) was administered IV and postcontrast, T(1)-weighted, axial images were acquired repetitively for up to 60 min. Images were analyzed to determine the spatial and temporal evolution of the intensity enhancement. A statistical decision mechanism was developed to objectively detect the enhancement. Strong and rapid enhancement was observed at the epicenter of injury, indicating a significant compromise in blood spinal cord barrier. The enhanced regions in each slice were combined to estimate the area and volume of the lesion. On the day of injury, around 85% of the total cord area at the epicenter showed enhancement within the first 15 min of Gd administration. At the same time, the enhanced volumes attained nearly 40% of the total cord volume and extended axially over 8 mm along the cord. These quantities decreased steadily with time, with a concomitant improvement in the motor functions. The volume of enhancement correlated highly with the neurobehavioral tests (r = -0.87). DCE-MRIs revealed small hyperintense regions distributed inside white matter about two weeks postinjury. Based on histology, these enhancements appear to represent new vessels with "leaky endothelium." Magn Reson Med 45:614-622, 2001.

Animals↗

PubMed2001

A pharmacokinetic model for quantitative evaluation of spinal cord injury with dynamic contrast-enhanced magnetic resonance imaging.

A multicompartment pharmacokinetic model was proposed to quantitatively describe the distribution of the contrast agent gadopentetate-dimeglumine (Gd) in an experimental spinal cord injury (SCI). Concentration of Gd was measured in different compartments with in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the acute phase of injury. The concentration data for each rat was fitted to the model to estimate transfer rates between different compartments. The results indicate: 1) lack of uptake of Gd in normal cord tissue, 2) rapid exchange of Gd between plasma and cerebrospinal fluid in both normal and injured cord tissues, and 3) slower uptake of Gd in injured cord. With this approach, it is possible to quantify the integrity of the blood-spinal cord barrier (BSCB) in vivo, evaluate the pathobiology of injured cord, assess the efficacy of interventions, and monitor the progression of injury with postinjury time.

Animals↗

PubMed2001

In vivo magnetic resonance microscopy of rat spinal cord at 7 T using implantable RF coils.

An inductively coupled implanted coil was designed for high-resolution magnetic resonance (MR) studies of rat spinal cord (SC) in vivo at 7 T. The practical issues involved in implementation of the coil at high fields are discussed, and the adjustment of various parameters for optimizing coil performance are described. The utility of the coil was demonstrated with anatomical, magnetization transfer, diffusion tensor imaging, and proton MR spectroscopy (MRS).

Animals↗

PubMed2001

United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates. Multiple Sclerosis Study Group and the MRI Analysis Center.

After the placebo-controlled extension of the pivotal US trial of glatiramer acetate for the treatment of relapsing multiple sclerosis ended, 208 participants entered an open-label, long-term treatment protocol Magnetic resonance imaging (MRI) was added to the planned evaluations of these subjects to determine the consequences of long-term treatment on MRI-defined pathology and evaluate its clinical correlates. Of the 147 subjects that remained on long-term follow-up, adequate images were obtained on 135 for quantitative MRI analysis. The initial imaging sessions were performed between June 1998 and January 1999 at 2,447 +/- 61 days (mean +/- standard deviation) after the subject's original randomization. Clinical data from a preplanned clinical visit were matched to MRI within 3 +/- 51 days. At imaging, 66 patients originally randomized to placebo (oPBO) in the pivotal trial had received glatiramer acetate for 1,476 +/- 63 days, and 69 randomized to active treatment with glatiramer acetate (oGA) were on drug for 2,433 +/- 59 days. The number of documented relapses in the 2 years prior to entering the open-label extension was higher in the group originally randomized to placebo (oPBO=1.86 +/- 1.78, oGA=1.03 +/- 1.28; P=0.002). The annualized relapse rate observed during the open-label study was similar for both groups (oPBO=0.2 7, +/- 0.45 oGA=0.28 +/- 0.40), but the reduction in rate from the placebo-controlled phase was greater for those beginning therapy with GA (oPBO reduced by 0.66 +/- 0.71, oGA reduced by 0.23 +/- 0.58; P=0.0002). One or more gadolinium enhancing lesions were found in 27.4% of all patients (number of distinct enhancements=1.16 +/- 2.52, total enhanced tissue volume=97 +/- 26 microl). The risk of having an enhancement was higher in those with relapses during the open-label extension (odds ratio 4.65, 95% confidence interval (CI) 2.0 to 10.7; P=0.001). The odds for finding an enhancement was 2.5 times higher for those patients originally randomized to placebo (CI 1.1 to 5.4; P=0.02) compared to those always on glatiramer acetate. MRI-metrics indicative of chronic pathology, particularly measures of global cerebral tissue loss (atrophy), were uniformly worse for those originally on placebo. These observations enrich our long-term follow up of the clinical consequences of treatment with glatiramer acetate to include its apparent effects on MRI-defined pathology. They show that the effect of glatiramer acetate on enhancements is definite, but modest, consistent with the drug's described mechanisms of action, and that a delay in initiating treatment results in progression of MRI-measured pathology that can be prevented.

Adult↗

PubMed2001

Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging.

Pathologically defined abnormalities in the cortical gray matter (GM) are well described in multiple sclerosis (MS) but are infrequently seen by conventional magnetic resonance imaging (MRI). We systematically evaluated 52 relapsing-remitting MS patients and 20 normal volunteers with high resolution MRI and short echo proton magnetic resonance spectroscopic imaging (MRSI). Individual tissue contributions to the spectroscopic voxels were estimated based on MRI that incorporated both CSF suppression and magnetization transfer, or double inversion images in which both CSF and GM were suppressed. Strong resonances in the 0.8 to 1.5 p.p.m. spectral region were observed in 13 MS patients. Image segmentation based on the MRI characteristics of tissues contributing to the spectroscopic voxels showed that these additional peaks originated mainly from GM. The presence of these additional peaks suggests that the normal appearance GM on MRI, is biochemically abnormal in a substantial proportion of relapsing-remitting MS patients.

Adult↗

PubMed2000

Linomide in relapsing and secondary progressive MS: part II: MRI results. MRI Analysis Center of the University of Texas-Houston, Health Science Center, and the North American Linomide Investigators.

OBJECTIVE: To determine the safety and efficacy of roquinimex (linomide) in the management of relapsing-remitting and secondary progressive MS as monitored by MRI. BACKGROUND: Preclinical studies and several short term randomized trials of linomide suggested clinical and MRI-measured benefits with acceptable risk for closely followed MS patients. METHODS: The North American Linomide Trial formally screened 853 individuals for relapsing or secondary progressive, clinically definite MS; recent disease activity or progression; and an Expanded Disability Status Scale score at entry of 3.0 to 6.5 inclusive. MRI was obtained on 811 subjects at pre-enrollment, 718 cases at enrollment, and then at three monthly intervals until the trial was prematurely terminated for unacceptable toxicity. RESULTS: Enhancement was found on 40.2% of 718 entry scans. Statistically robust correlations were found between clinical demographic data and several entry MRI measures including CSF volume, a reflection of brain atrophy. Assessment of the effect of treatment on MRI-measured disease was limited by early trial termination. However, active treatment for 3 months reduced the proportion of patients with one or more enhancements. An exploratory analysis suggested that 2.5 mg was the most active of three doses tested in limiting the total volume of enhanced tissue, the proportion of MRI-defined lesions designated as "black holes," and by a novel MRI composite disease measure. CONCLUSIONS: The short term signature of the effect of linomide on MRI-measured aspects of the disease suggests that safer drugs of this class might be useful in the management of MS. The use of a composite index of the heterogeneous nature of the pathology of MS as captured by MRI may have merit as an outcome measure in clinical trials.

Adjuvants, Immunologic↗

PubMed2000

Spatial and temporal evolution of hemorrhage in the hyperacute phase of experimental spinal cord injury: in vivo magnetic resonance imaging.

To follow the spatial and temporal evolution of hemorrhage, in vivo MRI studies of experimental spinal cord injury (SCI) were performed on 17 rats in the very acute phase (hyperacute), starting as early as 9 min and continued up to 400 min posttrauma. Axial MR images were processed slice by slice over a 21 mm length around the epicenter of the injury. The data were analyzed statistically and fitted to an empirically derived function to characterize the spatial and temporal evolution of hemorrhage. The results indicated that 1) the initial hemorrhage in the very early phase of the injury area covered 12.5% of the total cord area and subsequently increased with a time constant of 700 min, 2) a major portion of the hemorrhage was concentrated spatially within the 4 mm distance from the epicenter, 3) the volume of hemorrhage normalized to its initial value increased linearly at a rate of approximately 0.0015 min(-1), and 4) edema was observed at the gray- and white-matter junction as early as 12 min postinjury. In general, edema appeared to be focal and scattered in this phase of the injury, which made its quantification unreliable on MRI.

Acute Disease↗

PubMed1999

In vivo diffusion tensor imaging of rat spinal cord with echo planar imaging.

The in vivo apparent diffusion tensor (ADT) of spinal cord was measured in nine rats at 2.0 T using an interleaved multi-shot echo planar imaging (EPI) diffusion sequence. A technique that combines sliding acquisition and phase correction, based on a calibration scan, to reduce ghosting artifacts in the images introduced by the strong diffusion-sensitizing gradients was described. Two rotationally invariant parameters, the trace (actually trace/3, to be consistent with the published values) and the lattice anisotropy index (LAI) were estimated from the ADT. In in vivo cords, the mean white matter (WM) trace value (1.05 +/- 0.13 x 10(-3) mm(2)/sec) was found to be significantly higher than the gray matter (GM) trace (0. 84 +/- 0.12 x 10(-3) mm(2)/sec, p < 0.0025). Significant anisotropic diffusion was observed in both WM and GM, with greater anisotropy in the WM (LAI=0.59 +/- 0.04) than in the GM (LAI=0.47 +/- 0.06, p < 0. 0001). These results are in agreement with the in vivo values determined using the conventional spin-echo sequence. Magn Reson Med 42:300-306, 1999.

Animals↗

PubMed1999

In vivo diffusion characteristics of rat spinal cord.

Complete apparent diffusion tensor (ADTs) of spinal cord was measured in vivo in nine rats at 2.0 T. Two rotationally invariant parameters, the trace, which is a measure of the mean diffusivity, and the lattice index (LI), which reflects the degree of orientation coherence of tissue, have been estimated from the ADT. The mean white matter (WM) trace value (3.05 +/- 0.26 mm2/sec) was found to be substantially higher than the gray matter (GM) trace (2.36 +/- 0.39 mm2/sec), in contrast with the published results on fixed, excised cord. Statistically significant anisotropic diffusion was observed in both WM and GM, with greater anisotropy in the WM (LI = 0.67 +/- 0.06) than in the GM (LI = 0.51 +/- 0.05).

Animals↗

PubMed1998

Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis.

Serial magnetic resonance (MR) studies that included proton MR spectroscopic imaging (MRSI), contrast-enhanced MR imaging (MRI), and lesion volumetric studies were performed on 25 multiple sclerosis (MS) patients with mild to modest clinical deficits. Each patient was scanned at varying intervals for up to 2 years, resulting in a total of 124 usable MR sessions. In these longitudinal studies, metabolic changes were observed on MRSI for some subjects before the appearance of lesions on MRI scanning. Regional changes in metabolite levels were observed to be dynamic and reversible in some patients. Transient changes in N-acetylaspartate (NAA) levels were sometimes found in acute plaques and indicate that a reduced NAA level does not necessarily imply axonal loss. An inverse correlation between the average NAA within the spectroscopic volume and the total lesion volume in the whole brain was observed. This negative correlation implies that NAA can serve as an objective marker of the disease burden. Strong lipid peaks in the absence of gadolinium enhancement and MRI-defined lesions were observed in 4 patients. This observation suggests that demyelination can occur independent of perivenous inflammatory changes and supports the presence of more than one pathophysiological process leading to demyelination in MS.

Adult↗

PubMed1998

Automatic segmentation of gadolinium-enhanced multiple sclerosis lesions.

Automatic detection and quantitation of contrast-enhanced lesions on MRI is expected to be useful in characterizing the disease state in multiple sclerosis (MS). The enhancing structures such as cerebral vasculature and regions with no blood-brain barrier complicate automated analysis of lesion enhancement. A pulse sequence that incorporates both stationary and marching saturation bands and gradient dephasing is described for suppressing the enhancements within the cerebral vasculature. A postprocessing technique based on automatic image segmentation is implemented for eliminating enhancing structures such as choroid plexus. All MS lesions larger than 5 mm3 have been successfully identified. The automated analysis produced no false-positives or false-negative lesions above this volume in 13 patients with MS who were evaluated using the acquisition and evaluation techniques described.

Algorithms↗

PubMed1998

Volumetric analysis of white matter, gray matter, and CSF using fractional volume analysis.

Quantitative cerebral tissue volumes may be useful for an objective assessment of pathological changes in brain. Accurate determination of tissue volumes is complicated, however, by the partial volume averaging (PVA) effect. We have, therefore, developed a new pulse sequence that minimizes the PVA through the use of inversion-recovery (IR) and double inversion-recovery (DIR) techniques. This pulse sequence simultaneously acquires four different sets of images to provide the necessary information for volumetric analysis and reduces potential spatial misregistration of images due to patient motion. The image sets acquired from the proposed pulse sequence are 1) gray matter visible, 2) white matter visible, 3) FLAIR, and 4) fast spin-echo proton-density weighted images. An algorithm has been implemented to correct for differential T1-weighting and for tissue quantitation.

Artifacts↗