Rao P. Gullapalli

Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury.

Diffusion Kurtosis Imaging (DKI) provides quantifiable information on the non-Gaussian behavior of water diffusion in biological tissue. Changes in water diffusion tensor imaging (DTI) parameters and DKI parameters in several white and gray matter regions were investigated in a mild controlled cortical impact (CCI) injury rat model at both the acute (2 h) and the sub-acute (7 days) stages following injury. Mixed model ANOVA analysis revealed significant changes in temporal patterns of both DTI and DKI parameters in the cortex, hippocampus, external capsule and corpus callosum. Post-hoc tests indicated acute changes in mean diffusivity (MD) in the bilateral cortex and hippocampus (p<0.0005) and fractional anisotropy (FA) in ipsilateral cortex (p<0.0005), hippocampus (p=0.014), corpus callosum (p=0.031) and contralateral external capsule (p=0.011). These changes returned to baseline by the sub-acute stage. However, mean kurtosis (MK) was significantly elevated at the sub-acute stages in all ipsilateral regions and scaled inversely with the distance from the impacted site (cortex and corpus callosum: p<0.0005; external capsule: p=0.003; hippocampus: p=0.011). Further, at the sub-acute stage increased MK was also observed in the contralateral regions compared to baseline (cortex: p=0.032; hippocampus: p=0.039) while no change was observed with MD and FA. An increase in mean kurtosis was associated with increased reactive astrogliosis from immunohistochemistry analysis. Our results suggest that DKI is sensitive to microstructural changes associated with reactive astrogliosis which may be missed by standard DTI parameters alone. Monitoring changes in MK allows the investigation of molecular and morphological changes in vivo due to reactive astrogliosis and may complement information available from standard DTI parameters. To date the use of diffusion tensor imaging has been limited to study changes in white matter integrity following traumatic insults. Given the sensitivity of DKI to detect microstructural changes even in the gray matter in vivo, allows the extension of the technique to understand patho-morphological changes in the whole brain following a traumatic insult.

Functional MRI determination of a dose-response relationship to lower extremity neuromuscular electrical stimulation in healthy subjects

Abstract.Although empirical evidence supports the use of neuromuscular electrical stimulation (NMES) to treat physical impairments associated with stroke, the mechanisms underlying the efficacy of this modality are poorly understood. Recent studies have employed functional imaging to investigations of brain responses to median nerve stimulation. These studies suggest a dose-response relationship may exist between selected stimulation parameters and hemodynamic responses in sensorimotor regions. However, substantial gaps exist in this literature. The present study was designed to address these deficiencies. Ten healthy subjects participated. In phase one, four stimulus intensity levels were established: (1) sensory threshold [Th], (2) (MM−Th)×0.333+Th [low-intermediate level, LI], (3) (MM−Th)×0.666+Th [high-intermediate level, HI], and (4) maximal motor (MM). In phase two, subjects were scanned using a spiral-echoplanar imaging technique at each stimulus level. Image sets were analyzed to determine hemodynamic responses at the highest Pearson correlation level (r) ascertained for each of five areas of interest (AOI): (1) primary sensory, (2) primary motor, (3) cingulate gyrus, (4) thalamus, and (5) cerebellum. ANOVA demonstrated significant main effects for BOLD signal amplitude (p<0.05) changes in all AOI. Similarly, ANOVA showed significant differences in the volume of activation (p<0.05) with increasing stimulus intensity in four AOI. Secondary analyses of pooled data showed increasing probabilities of activation at higher stimulus intensities within each AOI. Collectively, these data indicate a dose-response relationship exists between lower extremity NMES and brain activation in specific neural regions. The current results, while limited in their generalizability, are foundational for future studies of interventions using NMES.

Diffusion Tensor MR Imaging in Cervical Spine Trauma

BACKGROUND AND PURPOSE: Our aim was to investigate the extent and severity of changes in spinal cord diffusion tensor imaging (DTI) parameters in patients with cervical cord injury. MATERIALS AND METHODS: DTI was performed in 20 symptomatic patients (mean, 45.7 ± 17.7 years of age; 2 women, 18 men) with cervical spine trauma and 8 volunteers (mean, 34.2 ± 10.7 years of age; 6 men, 2 women). The whole cord and regional apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR) of patients and volunteers were compared. DTI parameters were calculated in 16 patients. MR imaging demonstrated hemorrhagic cord contusions (n = 6), nonhemorrhagic cord contusions (n = 4), and soft-tissue injury (n = 6). Medical records were reviewed for extent of neurologic deficit. RESULTS: Regional ADC values differed significantly between upper and mid and upper and lower (both, P < .004) cervical cord sections. FA was significantly different between upper and lower sections (P < .03). Whole cord ADC values were significantly lower in patients than in volunteers (P < .0001). Whole spine FA was not significantly decreased in patients (P < .06). ADC and FA values were significantly decreased at injury sites when compared with volunteers (P < .031 and .0001, respectively). The greatest differences in whole cord ADC, FA, RA, and VR were in patients with hemorrhagic cord contusions compared with healthy volunteers (P < .0001, .003, .0005, and .008, respectively). CONCLUSION: DTI parameters are sensitive markers of cervical cord injury, with ADC showing the greatest sensitivity. Changes in DTI parameters are most marked at injury sites and reflect the severity of cord injury.

AAPM/RSNA physics tutorial for residents: MR artifacts, safety, and quality control.

Artifacts in magnetic resonance (MR) imaging result from the complex interaction of contemporary imager subsystems, including the main magnet, gradient coils, radiofrequency (RF) transmitter and receiver, and reconstruction algorithm used. An understanding of the sources of artifacts enables optimization of the MR imaging system performance. The increasing clinical use of very high magnetic field strengths, high-performance gradients, and multiple RF channels also mandates renewed attention to the biologic effects and physical safety of MR imaging. Radiologists should be aware of the potential physiologic effects of prolonged exposure to magnetic fields, acoustic noise, and RF energy during MR imaging and should use all the available methods for avoiding accidents and adverse effects. Imaging equipment should be regularly tested and monitored to ensure its stability and the uniformity of its functioning. Newly installed or upgraded MR systems should be tested by a physicist or qualified engineer before use. In addition, the authors recommend participation in the MR imaging accreditation program of the American College of Radiology to establish the initial framework for an adequate quality assurance program, which then can be further developed to fulfill local institutional needs.

Modeling the motion of the internal tongue from tagged cine-MRI images

A new technique, tagged Cine-Magnetic Resonance Imaging (tMRI), was used to develop a mechanical model that represented local, homogeneous, internal tongue deformation during speech. The goal was to infer muscle activity within the tongue from tissue deformations seen on tMRI. Measurements were made in three sagittal slices (left, middle, right) during production of the syllable /ka/. Each slice was superimposed with a grid of tag lines, and the approximately 40 tag line intersections were tracked at 7 time-phases during the syllable. A local model, similar to a finite element analysis, represented planar stretch and shear between the consonant and vowel at 110 probed locations within the tongue. Principal strains were calculated at these locations and revealed internal compression and extension patterns from which inferences could be drawn about the activities of the Verticalis, Hyoglossus, and Superior Longitudinal muscles, among others.

Test-retest reliability estimation of functional MRI data.

Functional magnetic resonance imaging (fMRI) data are commonly used to construct activation maps for the human brain. It is important to quantify the reliability of such maps. We have developed statistical models to provide precise estimates for reliability from several runs of the same paradigm over time. Specifically, our method extends the premise of maximum likelihood (ML) developed by Genovese et al. (Magn Reson Med 1997;38:497–507) by incorporating spatial context into the estimation process. Experiments indicate that our methodology provides more conservative estimates of true positives compared to those obtained by Genovese et al. The reliability estimates can be used to obtain voxel‐specific reliability measures for activated as well as inactivated regions in future experiments. We derive statistical methodology to determine optimal thresholds for region‐ and context‐specific activations. Empirical guidelines are also provided on the number of repeat scans to acquire in order to arrive at accurate reliability estimates. We report the results from experiments involving a motor paradigm performed on a single subject several times over a period of 2 months. Magn Reson Med 48:62–70, 2002.

Early Microstructural and Metabolic Changes following Controlled Cortical Impact Injury in Rat: A Magnetic Resonance Imaging and Spectroscopy Study

Understanding tissue alterations at an early stage following traumatic brain injury (TBI) is critical for injury management and limiting severe consequences from secondary injury. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H MRS) at 2 and 4 h following a controlled cortical impact injury in the rat brain using a 7.0 Tesla animal MRI system and compared profiles to baseline. Significant decrease in mean diffusivity (MD) and increased fractional anisotropy (FA) was found near the impact site (hippocampus and bilateral thalamus; p<0.05) immediately following TBI, suggesting cytotoxic edema. Although the DTI parameters largely normalized on the contralateral side by 4 h, a large inter-individual variation was observed with a trend towards recovery of MD and FA in the ipsilateral hippocampus and a sustained elevation of FA in the ipsilateral thalamus (p<0.05). Significant reduction in metabolite to total creatine ratios of N-acetylaspartate (NAA, p=0.0002), glutamate (p=0.0006), myo-inositol (Ins, p=0.04), phosphocholine and glycerophosphocholine (PCh+GPC, p=0.03), and taurine (Tau, p=0.009) were observed ipsilateral to the injury as early as 2 h, while glutamine concentration increased marginally (p=0.07). These metabolic alterations remained sustained over 4 h after TBI. Significant reductions of Ins (p=0.024) and Tau (p=0.013) and marginal reduction of NAA (p=0.06) were also observed on the contralateral side at 4 h after TBI. Overall our findings suggest significant microstructural and metabolic alterations as early as 2 h following injury. The tendency towards normalization at 4 h from the DTI data and no further metabolic changes at 4 h from MRS suggest an optimal temporal window of about 3 h for interventions that might limit secondary damage to the brain. Results indicate that early assessment of TBI patients using DTI and MRS may provide valuable information on the available treatment window to limit secondary brain damage.

Default Mode Network Interference in Mild Traumatic Brain Injury – A Pilot Resting State Study

In this study we investigated the functional connectivity in 23 Mild TBI (mTBI) patients with and without memory complaints using resting state fMRI in the sub-acute stage of injury as well as a group of control participants. Results indicate that mTBI patients with memory complaints performed significantly worse than patients without memory complaints on tests assessing memory from the Automated Neuropsychological Assessment Metrics (ANAM). Altered functional connectivity was observed between the three groups between the default mode network (DMN) and the nodes of the task positive network (TPN). Altered functional connectivity was also observed between both the TPN and DMN and nodes associated with the Salience Network (SN). Following mTBI there is a reduction in anti-correlated networks for both those with and without memory complaints for the DMN, but only a reduction in the anti-correlated network in mTBI patients with memory complaints for the TPN. Furthermore, an increased functional connectivity between the TPN and SN appears to be associated with reduced performance on memory assessments. Overall the results suggest that a disruption in the segregation of the DMN and the TPN at rest may be mediated through both a direct pathway of increased FC between various nodes of the TPN and DMN, and through an indirect pathway that links the TPN and DMN through nodes of the SN. This disruption between networks may cause a detrimental impact on memory functioning following mTBI, supporting the Default Mode Interference Hypothesis in the context of mTBI related memory deficits.

Design and Control of a 1-DOF MRI-Compatible Pneumatically Actuated Robot With Long Transmission Lines

This paper presents the design and control of an MRI-compatible 1-DOF needle-driver robot and its precise position control using pneumatic actuation with long transmission lines. MRI provides superior image quality compared to other imaging modalities, such as computed tomography or ultrasound, but imposes severe limitations on the material and actuator choice (to prevent image distortion) due to its strong magnetic field. We are primarily interested in developing a pneumatically actuated breast biopsy robot with a large force bandwidth and precise targeting capability during RF ablation (RFA) of breast tumor, and exploring the possibility of using long pneumatic transmission lines from outside the MRI room to the device in the magnet to prevent any image distortion whatsoever. This paper presents a model of the entire pneumatic system. The pneumatic lines are approximated by a first-order system with time delay, since its dynamics are governed by the telegraph equation with varying coefficients and boundary conditions, which cannot be solved precisely. The slow response of long pneumatic lines and valve subsystems make position control challenging. This is further compounded by the presence of nonuniform friction in the device. Sliding-mode control (SMC) was adopted, where friction was treated as an uncertainty term to drive the system onto the sliding surface. Three different controllers were designed, developed, and evaluated to achieve precise position control of the RFA probe. Experimental results revealed that all SMCs gave satisfactory performance with long transmission lines. We also performed several experiments with a 3-DOF fiber-optic force sensor attached to the needle driver to evaluate the performance of the device in the MRI under continuous imaging.

Correlation of MR Diffusion Tensor Imaging Parameters with ASIA Motor Scores in Hemorrhagic and Nonhemorrhagic Acute Spinal Cord Injury

This study investigated correlations between American Spinal Injury Association (ASIA) clinical injury motor scores in patients with traumatic cervical cord injury and magnetic resonance (MR) diffusion tensor imaging (DTI) parameters. Conventional imaging and DTI were performed to evaluate 25 patients (age, 39.7±13.9 years; 4 women, 21 men) with blunt spinal cord injury and 11 volunteers (age, 31.5±10.7 years; 3 women, 8 men). Cord contusions were hemorrhagic (HC) in 13 and non-hemorrhagic (NHC) in 12 patients. The spinal cord was divided into three regions to account for spatial and pathological variation in DTI parameters. Comparisons of regional and injury site mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity ( λ(⊥)), and longitudinal diffusivity ( λ(‖)) were made with control subjects. ASIA motor scores were correlated with DTI using linear regression analysis. HC and NHC patients showed significant reduction (p<0.001) in MD and λ(‖) in all three regions. At the injury site, significant decreases in FA and λ(‖) were seen for both injury groups (p<0.001). λ(⊥) values were significantly increased only for patients with NHC (p<0.05). Significant reduction in FA and λ(‖) (p<0.0001) was observed at the whole cord level between the injured (NH and NHC) and control groups. Within the NHC group, strong correlations were observed between ASIA motor scores and average MD, FA, λ(⊥), and λ(‖) at the injury site. However, no correlation was observed within the HC group between any of the DTI parameters and ASIA motor scores. DTI parameters reflect the severity of spinal cord injury and correlate well with ASIA motor scores in patients with NHC.