Access Type

Open Access Thesis

Date of Award

January 2014

Degree Type

Thesis

Degree Name

M.S.

Department

Biomedical Engineering

First Advisor

Zhifeng Kou

Abstract

CEREBRAL HEMODYNAMIC CHANGES IN MILD TRAUMATIC BRAIN INJURY AT THE ACUTE STAGE

by

Hardik J. Doshi

May 2014

Advisor: Dr. Zhifeng Kou

Major: Biomedical Engineering

Degree: Master of Science

There are more than 1.7 million reported traumatic brain injury (TBI) cases every year in the United States alone. Out of all these, more than 85% are mild TBI (mTBI) and it has significant socio-economic impacts. The motivation towards this study is to measure changes in the arterial cerebral blood flow (CBF) and venous oxygen saturation by combining Arterial Spin Labeling (ASL) and Susceptibility Weighted Imaging and Mapping (SWIM) techniques and to get a global picture of brain hemodynamic at the acute stage.

The main criteria for patient recruitment were the definition of mTBI by American Congress of Rehabilitation Medicine (ACRM) and Glasgow Coma Scale (GCS) of 13-15 at the time of arrival. Patients were scanned on 3T Siemens VERIO scanner with 32-channel head coil. Fourteen patients were scanned for SWI, among which 9 also had ASL. Nine patients had 1-month follow-up. The technical parameters for ASL were TR/TE of 2830/11 ms, flip angel of 90 degrees, with in-plane resolution of 4x4x4 and field of view of 384x384. SWI sequence was acquired using TR/TE 30/20 ms, flip angel of 20 degrees and field of view of 256x256 and in-plane resolution of 0.5x1x2. ASL data were processed to measure cerebral blood flow in Thalamus, Striatum, Frontal, Occipital, Parietal and Temporal lobes. The normalized ASL data was registered to the T1 template and the lobe/structure specific ROIs were projected back to the native space using inverse transform. The Wake Forest University (WFU) Pickatlas was used to get the reference ROIs. The cerebral blood flow values were recorded in the native space. SWIM processing was performed on the SWI data. Blood oxygen saturation in 8 major veins was measured on SWIM images. Semi-automated ROI analysis was performed and intra-reader and inter-reader test-retest were performed with high correlation. Student's t-test was performed in both ASL and SWI data analysis to compare the patient and control group.

Patient group showed significant lower SAC score than control group (p=0.05). The difference is more significant in delayed recall (p=0.02). In SWIM data, two major veins, left thalamo-striate vein and right basal vein of Rosenthal showed significantly lower oxygen saturation at acute stage than controls. ASL data shows significantly higher cerebral blood flow in the Striatum at the acute stage. This study shows that, after head injury, the increased cerebral blood flow is followed by more oxygen left in the venous side of the same striatum region. This suggests that there might be some deficiency in that part of the brain in which condition brain works hard and generates higher demand of blood supply. Weather the amount of changes in cerebral blood flow is in proportion with the increased oxygen saturation in the veins needs to be studied in more details. Changes in CMRO2 at the acute stage and variations in brain activity during this stage also need to be studied more comprehensively.

Volumetric analysis of cingulum in retired NFL players: Its relationship with NFL experience and subjects' cognitive and functional performance

by

Hardik J. Doshi

May 2014

Advisor: Dr. Zhifeng Kou

Major: Biomedical Engineering

Degree: Master of Science

There are 1.6-3.8 million sports concussions recorded in United States each year. Especially athletes of American football, Hockey, wrestling and boxing are more prone to concussion. After concussion or mild traumatic brain injury (mTBI), subjects may present a constellation of post concussion symptoms (PCS). Further, chronic traumatic encephalopathy (CTE) has been also reported related with sports concussion. It has been reported that cingulum cortex has been reported as susceptible to injury after trauma. The main motivation behind this study is to investigate the effects of multiple traumas on the volumes of anterior and posterior cingulum cortex (ACC & PCC) and determine its effects on Neuropsych and functional test scores. 45 retired National Football League (NFL) players were scanned. The average age of the players was 45.6+9.30 years. Data from each player's playing career including duration of professional, college and high school football career and number of concussions and dings each player had suffered were recorded. The MRI data was acquired on Siemens 1.5 T magnet. The parameters of the T1 sequence were as following: TR/TE = 2000/4.84 ms, Flip angle = 8 degrees, Bandwidth =160 Hz/Px, Field of view was 512x512, Slice thickness of 2 mm and resolution was 0.5x0.5x2 mm3. Beck Depression Inventory (BDI_II) and Mini Mental State Examination (MMSE) scores were recorded. BDI_II scores were 9.6 + 9.25 and MMSE scores were 28.35 + 1.27 for the group.

All the subjects' images were non-linearly registered to JHU Talairach T1 template using SPM8. A set of predefined ROIs for JHU Talairach T1 template from ROIEditor (Version 1.6, mristuio.org) was used. Once all the subjects are in the standard template space, an inverse transform matrix was applied to all the subjects. Same matrix was applied to the predefined ROIs in template space. As a result all the subjects as well as ROIs are back into the native space. IBM analytical tool SPSS 21.0 (SPSS, Inc., Chicago IL) was used for the statistical analysis. Bivariate correlations between volumes of ACC & PCC were checked for any correlation with Neuropsych test scores. In the second part, mediation analysis using "PROCESS" by Dr. Hayes (model 4) was performed to see any mediation effect of volumes of ACC and PCC on the relationship between players' career data and neuropsych scores.

Volume of PCC partially mediates the relationship between number of years played in NFL and BDI_II score (Total effect significance p=0.003). Volume of ACC did not mediate any correlation significantly. In bivariate correlation analysis, Volume of PCC is negatively correlated with the BDI_II score (p=0.001). Volume of ACC shows tendency in inverse correlation with BDI_II score (p=0.023). Number of years played in NFL is directly correlated with number of concussions suffered in NFL (p=0.00001). Players are susceptible to more concussion when they play for longer duration. Mediation model explains that number of years in NFL has some effects on PCC volume, which in turn affects on depression score. Possible mechanism could be loss of neurons due initial concussion. This would be aggravated by more concussions, ultimately leading to change in volume. Cingulum cortex is emotional hub. So changes in PCC volume may reflect on depression score. Also ACC and PCC volumes have inverse correlation with BDI_II score. This also strengthens the hypothesis. This is in line with few earlier studies suggesting that more detailed research is required to look into the role of cingulum cortex in CTE.

Hemorrhagic lesions and its clinical correlation based on venous and arterial damage in Traumatic Brain Injury

by

Hardik J. Doshi

May 2014

Advisor: Dr. Zhifeng Kou

Major: Biomedical Engineering

Degree: Master of Science

Traumatic Brain Injury (TBI) is a major cause of death and disability all over the world. Hemorrhagic blood is a clinical diagnosis biomarker. Susceptibility Weighted Imaging (SWI) is most sensitive non-invasive method to detect any bleed. During TBI veins and arteries undergo significant level of stresses and strains. It can easily cause a vessel wall to break down. Recovery after vessel breakage is significantly different depending on the type of vessel, location of the rupture and severity of the damage. The main objective of this study is to investigate the spatial relationship between hemorrhagic bleed and different types of vessels, e.g. veins vs. arteries, as well as its relationship with TBI patients' clinical and outcome information. A total of 28 TBI patients were recruited with written consent. Patients' group mean age was 40.51+15.72 years. Patients were scanned 360.19+490.21 days post injury. Mean Glasgow Coma Scale (GCS) score was 8.46+4.37. Mean Extended Glasgow Outcome Scale (GOSE) score was 6.21+1.54. All MRI data were collected on a 3-Tesla Siemens Verio scanner with a 32-channel radio frequency head coil (Siemens Medical Solutions, Erlangen, Germany). SWI parameters were: TR/TE of 30/20ms, Flip angle of 15 degree, bandwidth of 100 Hz/Px, field of view (FOV) of 256x256 mm2, 25% oversampling, slice thickness of 2 mm, total 64 slices, 20% distance factor, GRAPPA iPat factor of 2 and resultant voxel size of 0.5x1x2 mm3. All SWI images were analyzed using our in-house software SPIN. 4 slices (8mm) were minimally intensity projected (mIPed) onto one slice to visualize the continuity of vessels. In a robust semi-automatic approach, 25% of the mean background signals intensity was decided as a threshold to quantify volume. If a bleed is connected with a vein, it is being defined as venous bleed; otherwise, called free standing bleed. If more than 50% of bleeds in a patient is associated with veins, this patient would be classified as venous bleeding patient; otherwise, freestanding bleeding patient. IBM analytical tool SPSS 21.0 (SPSS, Inc., Chicago IL) was used for the statistical analysis. Correlations between number of bleeds and bleeding volume with GCS and GOS-E scores were performed. Group comparison was also performed using by using ANOVA. Groups were divided based on venous association of the bleed and freestanding bleeds.

Total number of lesions including freestanding bleeds, number of lesions associated with veins and volume of lesions associated with veins were inversely correlated with GCS (p = 0.009, 0.005 0.011 respectively). Number and volume of freestanding bleeds did not show any correlation with GCS or GOS-E. In group analysis, the group with more venous associated bleeds showed significantly high number of bleeds, lower GCS and higher GOS-E score (p=0.03,0.007,0.03 respectively). Also significantly high number of lesions were observed in the group with GCS lower than 9 with p=0.039. No significant lesion volume difference between the two groups with different GCS was observed.

Number and volume of the lesions associated with veins are inversely correlated with GCS score. Also, group with lower GCS has higher number of lesions. This suggests that number and volume of the lesions could be an indicator of the injury severity in early stages. Arteries face continuous high blood pressure compared to veins. So structurally they are more robust and contain more elastic fibers and smooth muscle. Higher number of bleeds associated with veins suggests higher degree of venous fragility. This is in line with earlier published data suggesting that arteries can withstand almost double amount of stress compared to veins before breaking down. The group with more free standing bleeds has worse GOS_E outcome score compared to the group with more venous associated bleeds. This might indicate that once damaged, recovery is slower on the arterial side. One possible explanation could be that unlike arterial system, venous system shows some degree of redundancy in blood drainage. But there is no `bypass' way for arterial blood supply. Few more comprehensive studies are required to observe the role of different vessels in the event of trauma and how different insults lead to different levels of injury severity and different outcomes. This could be very valuable information while assessing the injury severity at early stage and also in deciding future medication.

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