MINISTRY OF EDUCATION & TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES VU DUY LAM ESTIMATING PYRAMIDAL TRACT LESIONS AND SOME DIFFUSION TENSOR IMAGING INDEXS RELATED TO MOTOR FUNCTION IN ISCHEMIC STROKE PATIENTS Speciality : Medical Imaging Code : 62.72.01.66 SUMMARY OF THE THESIS HÀ NỘI - 2019 THIS THESIS IS FINISHED IN 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Name of supervisor: MD, PhD, Ass Prof Lam Khanh MD, Ass Prof Vu Long Reviewer 1: …………………………………………… Reviewer 2: …………………………………………… Reviewer 3: …………………………………………… The thesis will be upholded by hospital council at: h date month year 2018 Can find out more about this thesis in: National Library Library of 108 Institute of clinical Medical and Pharmaceutical sciences POSITION OF THE PROBLEM Importance of the problem: Cerebral infarction is a severe diease which is the 3rd most common cause of mortality in Viet Nam after cancer and myocardial infarction Ischemic stroke makes some serious sequelae, 50% alive patients got paralytic symptoms and depended on the helping of the community Motor paralysis is a symptom highly related to the damage of the pyramidal tract In the past, the diagnosis of the pyramidal injury mostly depended on the Babinski sign (+) The medical imaging of the pyramid was very difficult, because it had the same density and signal with the white matter in CT and MRI imagings The invention of DTI can display the pathway of nervers in the brain and applying this technique can evaluate the damage of the tract, study the relationship between the pyramidal damage with patient’s motor function recovery which help doctors to make a right prognosis, have an effective treatment stratery and reduce patient’s sequela Therefor, we performed this research: “Estimating pyramidal tract lesions and some Diffusion Tensor Imaging indexs related to motor function in ischemic stroke patients” in 108 Institute of Clinical Medical and Pharmaceutical Sciences, where had a specialist stroke center and a MRI 3.0 Tesla with DTI sequence Aim of the thesis Describe the imaging characteristics of the neural tract lesions in DTI inischemic stroke patients compared to normal people Estimate the relation between some DTI indexs to motor function in ischemic stroke patients Contribution of the thesis: This is the first research in Viet Nam about the damage of pyramidal tract in MRI Contribution in radiology: Develop a new technique in radiology Contribution in treatment: Help to prognose the chance of motor recovery to make an effective treatment strategy Presentation of the thesis The thesis comprises 116 pages, dealing with pages for Position of the Problem, 30 pages for the Overview, 17 pages for the Subjects and Research Method, 32 pages for the Study Results, 28 pages for the Discussion, pages for the Conclusions There are 45 tables, 18 charts, 28 images of the study design There are 114 references, including 13Vietnamese documents and 101 English documents Chapter 1: OVERVIEW 1.1 Anatomy The pyramidal tract is the most important motor pathway in the human brain The pyramidal tract includes both the motor cortex and the motor pathways 1.1.1 The motor cortex Classically the motor cortex is an area of the frontal lobe located in the anterior to the central sulcus It contains the primary motor cortex, the premotor cortex, the supplementary motor area 1.1.1.1 The primary motor cortex The primary motor cortex is located between the precentral sulcus and central sulcus include central gyrus and the paracentral lobule Anatomically, the precentral gyrus can be divided into four segments: the inferior segment, the middle segment, the superior segment, the paracentral segment In function, each the segment of the precentral gyrusis a functionl unit control a partof the body The inferior segment: functional unit of the face; the middle segment: functional unit of the hand and arm; the superior segmentfunctional unit of the trunk; the paracentral segment: functional unit of the leg 1.1.1.2 The premotor cortex: The premotor cortex is in front of the primary motor cortex, patially locate in the mesial aspect of hemisphere anterior to the paracentral lobule 1.1.1.3 The supplementary motor area The supplementary motor area (SMA) is located in the mesial aspect of the first frontal gyrus, anterior to the primary motor cortex of lower extremity and above the cingulate sulcus and behind the premotor cortex The SMA is linked with the contralateral SMA through the commissural fibers of the corpus callosum 1.1.2 Motor pathways Motor pathways or the pyramidal pathwaysinclude two components: the pyramidal tract or corticospinal tract and the corticonuclear fibers In function, the pyramidal tract controls muscle of the trunk, the corticonuclear fibers control muscles of the head, face and neck The pyramidal tract The origins and pathways of the pyramidal tract are fully decribed in the anatomy books, we would not repeat it In general, the pyramidal tract can be divided into two parts:Upper part (hemisphere part) shaped like a fan and lower part (from cerebral stem downwards) is cylinder in shape At present, with the DTI we can see the image of pyramidal tract from the cerebral cortex to the upper part of the medulla oblongata.The pyramidal tract is composed of approximately million axons of motor neuron Each neuron consists of a cell body, one or more dendrites and an axon The axon is the primary structure part of the tract Axons with myelin sheath are called myelinated appear white, masses of such axons form the fiber bundle CNS axons are myelinate by oligodendrocytes, which not provide a neurilemma Consequently, damaged CNS axon (the pyramidal tract) usually not regenerate to result Waller degeneration 1.2 Pathology 1.2.1 Cerebral infarction Acute stage: The necrosis process is formed, local edema of the brain, initiation is intracellular cytotoxic edemathen there were vasogenic edema and extracellularedema Subacute stage: In this stage, the process of repair and absorption of necrotic tissue, it takes place from the periphery towards the center of encephalomalacic area The result of this process is the formation of cyst with surrouding glial scars Chronic stage: The appearance of the fluid-filled cavity lined by astrocystes and glial scars, the sulci and ventricle is dilated, the gyri is shrinked Cerebral infarction in areas where the pyramid tract passes leads to damage in each segment passing through This process takes place in several stages, the last and most severe consequence is Waller degenerationin the far part of axon Neurotransmitter ability of axon is lost 1.2.2 Damaged pyramid tract The injury process will go through stages Stage 1: Manifested by physical interruption of the myelin sheath and axon Stage 2: Characterized by the destruction of the myelin sheath Stage 3: The myelin sheath almost disappeared, the glial tissue replaced the myelin sheath and axon degeneration Stage 4: Characterized by cerebral volume lost and atropic the white matter bundle (Waller degeneration) Morphologically, it can only detect an axon degeneration at stage Early manifestations of degeneration can only be detected by the change of FA and ADC indexes on DTI 1.3 Clinical diagnosis Patient clinical nerve symptoms help doctors to direct the diagnosis Besides, evaluating the area of lesion, clinicians need to measure the level of losing motion though patient muscle power and the recovery by mRankin scales -Evaluate clinical muscle power by MRC scales 1976 Display from 0-5 point: completely paralytic points: normal power - Evaluate the patient recovery by mRankin scales Prognosis by Rosso (2011): good recovery if mRankin ≤ 2, bad if > mRankin > Chapter 2: SUBJECTS AND RESEARCH METHODS 2.1 Subjects 2.1.1 Places and time The thesis was performed in the 108 Institute of Clinical Medical and Pharmaceutical Sciences from 2/1011 to 9/2016 2.1.2 Subjects * Selection criteria of patients - Paralytic patients diagnosed as brain infarct by MRI 3.0 Tesla in the 108 Institute of Clinical Medical and Pharmaceutical Sciences - Patients had one infarct lesion located in pyramidal tract in MRI - Patients was treated and had full records in the 108 Institute of Clinical Medical and Pharmaceutical Sciences - Non-resident patients were recovered motion function with the stardard process over year * Criteria of Comparation - Adults with every genders, none paralytic, none clinical symptoms - Non-abnormal imagings in MRI * Exclusion criteria - Patients is not available with selection criterias - Patiens with relapsed infart in clinical or CT scans 2.1.3 The sample size It is calculated by this formula: n   1 / pq d With level of confidenceis 99% (Z1-/2= 2,58), precisionis 0,1, the percentage of the damaged pyramidal tractis 44% according toresearchAli (2012) with 57,1% Following this formula, the sample size in this reseach is: N = 2,582 x 0,571 x 0,12/0,12 = 45 2.2 Methods of study 2.2.1 Study design Prospective studies, cross – sectional descriptive 2.2.2 Means of research - MRI Achieva 3.0 Tesla Phillips with 16 channel coils and DTI sequences - Software: Extended MR Workspace 2.2.3 The protocol of MRI examination - Perform MRI scout viewthrough the head - Examination the brain: take the axial slides from the base to the vertex along to the OM linewith these sequences T1W, T2W, FLAIR, DWI - Examination the pyramidal tract with DTI sequences 32 SENSE (TR: 10172 ms, TE: 93 ms) with EPI technique,the number of diffuse direction: 32; b: 1000s/mm2 ; matrix: 128 x 128, FOV: 230 x 230 mm; slide thickness mm, voxel size: 1,8 x 1,8 x mm - Tranfer data to the workstation 2.2.4 Protocol of analyzing data and reconstruction imagings - Build FA 2D color map - Reconstruction 3D of the pyramidal tract from FA color map 2.3 The criteria used in study 2.3.1 General characteristics - Comparation group: - Infarction group 2.3.2 DTI of pyramid tract in the comparation group - Departure of the tract, measurement of the tract in 3D - FA, ADC values of total pyramidal tract FA, ADC values of each tract: corona radiate, internal capsule, basal ganglia, thalamus, pons Corona radiata Internal capsule Midbrain a b c Pons infarct Medulla oblongata Hình 2.1 Illutration of brain shows ROIs of the CST for FA, ADC measurements Pons infacrt; a: top, b: center, c: bottom Source Zhang 2015 2.3.3 DT imagings in infarct patients - Imagings of infarction area: location, median area, median depth, FA, ADC - Imagings 2D, 3D of the pyramid tract on MRI - The degree of the damaged of the pyramid tract, relation between tract lesions and the level of paralytic - Relation between the characteristics of diffusion tensor indexs and the recovery after year 2.4 Collecting, handlingand analysis data 2.4.1 Collecting techniques 2.4.2 Tools to collect the information 2.4.3 Handling and analysis data Data is analysed by biomedical statistics method Analyse data by software SPSS16.0, Epi 3.5.4, Epicalc 2000.Value p < 0,05 is statistical significance Chapter 3: RESULTS 3.1 Clinical characteristics - Comparation group Age and gender: 52 people devided into 26 males and 26 females, the medium age is 41,4 ±15,4 No one is paralytic - Infarction group 3.1.1 General information - Gender The number of males are 45 people, account for 69,0% and 20 females, account for 31% Male/female: 2,2 -Age The medium age in this research is 63,3±12,9 The minium is 32 years and the maximum one is 92 years The median age is 65 years 3.1.2 Clinical symptoms 3.1.2.1 Time admission and time of treatment The medium time admission since having the first symptom The hyperacute is 5,1 ± 2,1 hours The acute is 17,2 ± 6,4 hours The subacute is 83,5 ± 41,4 hours The chronic is 384 ± 145,9 hours The medium time of treatment is 17 ± 5,9 days 3.1.2.2 The recovery after year Table 3.3 mRankin scores after year mRankin scores Total Number (n) Percentage % 11 17 11 57 5,3 19,3 29,8 19,3 8,8 5,3 12,3 100 3.2 Imagings characteristics in DTI 3.2.1 Pyramid tract DTI in comparation group 3.2.1.1 The size of the tract Table 3.5 The size of the tract in the both sides Side Right Left Index Voxel 818,8 ± 84,6 834,1 ± 82,2 Length (mm) 129,1 ± 11,4 127,8 ± 10,3 Number of fibres 498,9 ± 67,9 496,5 ± 35,8 p 0,35 0,54 0,82 3.2.1.2 DTI indexs of the tract Table 3.6 FA and ADC in the whole pyramidal tract Pyramidal tract Right Left p FA 0,530±0,089 0,512±0,070 0,25 ADC (10-3 mm2/s) 0,839±0,100 0,832±0,101 0,70 Indexs 11 3.2.3.2 Relation between the location of tract and the infarction Table 3.15 Relation between the location of tract and the infarction Involvement No (n) Partial (n) Total (n) Total (n) Location Corona radiata 15 Internal capsule Basal ganglia Thalamus 0 Midbrain Pons 10 13 Medulla oblongata 0 1 15 Area supplied by MCA Total 21 12 32 65 Table 3.16 Signal of the infarction in the tract showed in FA color map Normal Low signal Empty signal Total 3 12 2 28 25 15 13 15 65 Location Corona radiata Internal capsule Basal ganglia Thalamus Midbrain Pons Medulla oblongata Area supplied by MCA Total 12 Table 3.17 Compare the FA and ADC values in the infarction and the opposite side Pyramid tract FA ADC(10-3 mm2/s) The infarction (n=65) The opposite side (n=65) p 0,491± 0,073 0,846 ± 0,119 0,527 ± 0,046 0,899 ± 0,095 0,00 0,00 Table 3.18 Compare theFA, ADC, voxel ratio and the length of right pyramidal tract between the infarction group and comparation group Right tract Infarction Comparation group group p (n=30) (n=52) Ratio FA 0,506±0,06 0,530± 0,09 0,28 ADC 0,869±0,11 0,839±0,10 0,21 Voxel 477,1±61,38 818,8 ± 84,6 0,00 Length 118,5±21,7 129,1 ± 11,4 0,00 Number of fibres 121±116,2 498,9 ± 67,9 0,00 Table 3.19 Compare theFA, ADC voxel ratio and the length of left pyramidal tract between the infarction group and comparation group Left tract Infarction Comparation group group p (n=35) (n=52) Tỷ số FA ADC Voxel Length Number of fibres 0,476±0,082 0,827±0,127 487,6±282,4 110,6±25,8 99,6±98,5 0,512±0,071 0,832±0,101 834,1 ± 82,2 127,8 ± 10,3 496,5 ± 35,8 0,03 0,83 0,00 0,00 0,00 13 3.2.3.3 Damaged in infarction pyramidal tract segments in the hyperacute stage Table 3.20-21 Compare FA, ADC values between infarction pyramidal tract segments and the opposite side The opposite side (n=9) p Values Location Infarction (n=9) FA Center Top 0,525±0,210 0,438±0,181 0,694±0,104 0,512±0,150 0,07 0,39 Bottom 0,478±0,152 0,648±0,210 0,08 Center 0,567±0,111 0,736±0,062 0,00 Top 0,546±0,216 0,850±0,150 0,00 Bottom 0,762±0,180 0,648±0,210 0,26 ADC 3.2.3.4 Damaged in infarction pyramidal tract segments in the acute stage Table 3.22-23 Compare FA, ADC values between infarction pyramidaltract segments and the opposite side The opposite Infarction Location side p Values (n=20) (n=20) FA ADC Center 0,488±0,204 0,608±0,176 0,04 Top 0,544±0,153 0,509±0,136 0,43 Bottom 0,556±0,162 0,617±0,172 0,24 Center 0,613±0,202 0,747±0,114 0,01 Top 0,673±0,172 0,785±0,096 0,01 Bottom 0,698±0,176 0,815±0,175 0,03 14 3.2.3.5 Damaged in infacrtion pyramidal tract segments in the subacute stage Table 3.24-25.Compare FA, ADC values between infarction pyramidal tract segments and the opposite side The Infarction opposite Values Location p (n=33) side (n=33) 0,680±0,132 0,00 Center 0,507±0,236 0,585±0,118 0,00 Top 0,445±0,194 FA 0,667±0,176 0,16 Bottom 0,601±0,205 Center 0,620±0,227 0,725±0,212 0,05 Top 0,724±0,214 0,725±0,137 0,98 ADC Bottom 0,693±0,211 0,736±0,179 0,37 In this research, there were patients in the chronic stage The number of patients aren’t enough to perform comparation 3.2.4 Relation between the tract DTI indexs and the patient’s motor function after year Table 3.26 The degree of the tract lesion followingNelles (2008) Intact (n) Partial disruption (n) Complete disruption (n) Total Corona radiate 15 Internal capsule 3 Basal ganglia 2 Thalamus 2 Midbrain Pons 13 Medulla oblongata 1 Area supplied by MCA 6 15 Total 12 28 25 65 Statement Location 15 3.2.4.1 Relation between the degree of the tract damaging and the patient’s motor function after year Table 3.27 Relation between the degree of tract damaging and mRankin score after year Statement mRankin score Intact (n) Partial disruption(n) Complete disruption(n) Total 0 11 11 25 1 4 21 11 16 11 57 Total Table 3.28 Relation between the degree of the tract damaging and the motor recovery after year Statement Recovery Good Bad Total p Intact (n) Partial disruption(n) 11 Complete disruption(n) Total 17 21 30 27 57 17 25 0,005 Table 3.29 Comparing the recovery rate bettween the group intact tract and disruption tract Recovery Good Bad Total Intact 30 Disruption 21 25 27 Total 30 27 57 Statement 16 3.2.4.2 Relation between some clinical factors, DTI indexs and the patient motor function after year * Relation between some clinical factors and mRankin score after year Table 3.30 Relation between some clinical factors and mRankin score after year Correlation Factor coefficient p Spearman (r) Arm muscle power at the admission -0,29 0,01 Arm muscle power at the discharge -0,24 0,04 Leg muscle power at the admission -0,31 0,01 Leg muscle power at the discharge -0,18 0,09 * Relation between some tract damaged factors and mRankin score after year Table 3.32 Relation between some tract damaged factors and mRankin score after year Correlation Factor coefficient Spearman p (r) rFA ratio 0,06 0,32 Virtual fibre ratio -0,15 0,13 Length ratio -0,39 0,001 Voxel ratio -0,24 0,03 FA in the center -0,40 0,001 ADC in the center 0,10 0,23 FA in the bottom -0,23 0,04 ADC in the bottom 0,10 0,21 FA in the top 0,18 0,09 ADC in the top -0,02 0,44 17 * Relation between FA, ADC values in the tract damaged segment in the hyperacute and acute stages and the recovery after one year Table 3.33-37.Relation between FA, ADC values in the tract damaged segment in the hyperacute and acute stages and the recovery after one year Values FA ADC Location Good recovery (n=12) Bad recovery (n=14) p Center Bottom Top Center Bottom Top 0,588±0,232 0,616±0,159 0,603±0,192 0,628±0,205 0,661±0,128 0,672±0,162 0,473±0,220 0,616±0,150 0,556±0,139 0,574±0,244 0,643±0,086 0,626±0,190 0,36 0,99 0,63 0,64 0,78 0,61 * Relation between FA, ADC values in the tract damaged segment in the subacute stages and the recovery after one year Table 3.38-41 Relation between FA, ADC in the tract damaged segment in the subacute stages and the recovery after one year Values FA ADC Center Bottom Top Center Bottom Good recovery (n=17) 0,538±0,266 0,713±0,135 0,448±0,209 0,564±0,215 0,612±0,182 Top 0,708±0,238 Location Bad recovery (n=12) p 0,484±0,213 0,522±0,228 0,399±0,189 0,736±0,213 0,6165±0,214 0,62 0,01 0,17 0,07 0,96 0,741±0,203 0.69 In the good recovery, FA in the bottom is higher than the center, it has statistical significance (p=0,01) 18 * Prognose the motor recovery after year Table 3.44 Multivariateregression logistic in the good recovery following mRankin score after year mRS score after year Statistical Confidence significance interval95% (CI) (p) 0,75 0,355 4,209 Admission arm muscle power Odds Ratio (OR) 1,223 Discharge arm muscle power 0,592 0,89 0,465 1,946 Admission leg muscle power FA in the center lesion 1,439 14,284 0,51 0,14 0,481 0,392 4,304 521,136 FA in the bottom lesion 0,871 0,90 0,014 43,348 Lengthratio 5,881 0,005 2,399 14,420 Voxel ratio Pyramid tract disruption 1,329 1,099 0,69 0,92 0,327 0,138 5,394 8,754 Prognosis factors According to the multivariate regression model, among these prognosis factors, the length ratio between the infarction side and the opposite side is the only factor to evaluate the patient recovery after year with OR=5,881; p0,05) 4.2 MRI in the infarction area 4.2.1 Distribution according to the cerebral artery supplement Infarction in the middle cerebral artery supplement had the highet figures, with 55,4% (36 patients) Table 3.7 show that, the lowest percentage of infarct was in the area supplied by anterior choroidal artery 4.2.2 Location of infarct Table 3.8 shows that, most of brain infarct located in supratentorial with 73,8%.Pons infarction is often seen in the infratentorial (13/65 patients, with 20%) 4.2.3 The area and depth of the infarction The biggest medium infarction area supplied by MCA is 2568,1 mm2 The smallest area infarction is in medulla oblongata (57 mm2) (Table 3.9-10) In our statistics, there is no relation between the infarction area and the mRankin score after year (r=0,12; p>0,05) and it is also no relation between the infarction area and the level of arm paralysed (r = -0,23; p > 0,05) 20 In our research, the deapest infarction is located in area supplied by MCA (44,3 mm) and the most shallow area is in the pons (13,2 mm) Table 3.9-10 shows that it has statistically significant (p