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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA SYNOPSIS FOR REGISTRATION OF SUBJECT FOR DISSERTATION DIFFUSION WEIGHTED MAGNETIC RESONANCE IMAGING WITH APPARENT DIFFUSION COEFFICIENT MAPS FOR THE EVALUATION OF PATIENTS WITH ACUTE NEUROLOGICAL DEFICITS DR.SAMEEHA KHAN PG IN RADIODIAGNOSIS AL-AMEEN MEDICAL COLLEGE BIJAPUR 1 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES 1 Name of the candidate And Address (In block letters) 2. Name of the Institution 3 4 5 Course of study and subject Date of admission to course Title of the Topic 6 Brief resume of the intended work: 6.1 Need for the study 6.2 Review of literature 6.3 Objectives of the study Material and methods 7.1 Source of data 7.2 Method of collection of data( including sampling procedure if any) 7.3 Does the study require any investigations or interventions to be conducted on patients, humans or animals? If so please describe briefly. 7.4 Has ethical clearance been obtained from your institution in case of 7.3. 7.5 Patient’s Consent Form List of References (About 4-6) Signature of candidate 7 8 9 DR.SAMEEHA KHAN PG IN RADIODIAGNOSIS, DEPARTMENT OF RADIOLOGY, AL-AMEEN MEDICAL COLLEGE, BIJAPUR AL-AMEEN MEDICAL COLLEGE, BIJAPUR, KARNATAKA. M.D. RADIODIAGNOSIS MAY 2013. DIFFUSION WEIGHTED MAGNETIC RESONANCE IMAGING WITH APPARENT DIFFUSION COEFFICIENT MAPS FOR THE EVALUATION OF PATIENTS WITH ACUTE NEUROLOGICAL DEFICITS VIDE ANNEXURE – I VIDE ANNEXURE – II VIDE ANNEXURE – III VIDE ANNEXURE – IV VIDE ANNEXURE – IV VIDE ANNEXURE – V VIDE ANNEXURE – VI VIDE ANNEXURE – VII VIDE ANNEXURE – VIII 2 10 Remarks of the guide 11 Name & Designation(In block letters) 11.1 Guide TO ASSESS THE SIGNIFICANCE OF DIFFUSION WEIGHTED MAGNETIC RESONANCE IMAGING WITH APPARENT DIFFUSION COEFFICIENT MAPS FOR THE EVALUATION OF PATIENTS WITH ACUTE NEUROLOGICAL DEFICITS DR.RAMESH .V. MANKARE MD, DNB RADIODIAGNOSIS PROFESSOR, DEPARTMENT OF RADIOLOGY, AL-AMEEN MEDICAL COLLEGE, BIJAPUR 11.2 Signature 11.3 Co-Guide 11.4 Signature 11.5 Head of the Department DR.MUNEER AHMED MD. RADIODIAGNOSIS PROFESSOR AND HEAD DEPARTMENT OF RADIOLOGY, AL-AMEEN MEDICAL COLLEGE, BIJAPUR 11.6 Signature 12 12.1 Remarks of the chairman & Principal 12.2 Signature 3 ANNEXURE – I BRIEF RESUME OF THE INTENDED WORK:6.1 NEED FOR THE STUDY:Diffusion weighted imaging (DWI) is an MRI technique that quantifies the movement of water molecules at a cellular level. As the diffusion properties of water vary in areas of necrosis, high cellularity, inflammation and fibrosis, this technique is inherently sensitive to different pathologies1 and has become a well-established adjunct to standard sequences during the diagnosis of neurological deficits. Diffusion is affected by the biophysical properties of tissue cell organization (cell membranes, fibers and macromolecules), density, microstructure and microcirculation2. Intracellular water diffusion is more hindered than that in the extracellular spaces which are lacking natural barriers. Pathological processes which change the volume ratio or physical nature of intra- and extracellular spaces affect the diffusion of water molecules. Restricted or impeded diffusion is seen in tissues with high cellularity , e.g. tumors, abscesses, fibrosis and cytotoxic edema3. Relative free or unimpeded diffusion is encountered in tissues with low cellularity or tissues with disrupted cell membranes, for example in cysts and necrotic tissues3,4. Diffusion coefficients in DWI are reflected in the apparent diffusion coefficient (ADC, expressed in mm2/s).4,5,6 Regions with restricted mobility of water molecules yield a greater DW-MRI signal and appear bright. In apparent diffusion coefficient (ADC) maps, regions that contain high water mobility appear bright 4. Thus far DWI has been used primarily for the detection of acute cerebral infarction. However there are other applications in which DWI facilitates diagnostic purpose in the management 4 of neurological deficits as early diagnosis and treatment is necessary to prevent mortality and morbidity5. With DWI, Acute cerebral ischemia can be diagnosed within 1 hour of the onset of symptom , much earlier than T2 weighted images 6. This is essential, as intervention in stroke has a vital role during initial few hours. Diffusion weighted imaging(DWI)is one such pulse sequence which has emerged as a powerful adjunct to routine magnetic resonance evaluation ,providing a boost to lesion detection as well as tissue characterisation. 5 ANNEXURE – II 6.2 REVIEW OF LITERATURE:Diffusion weighted imaging (DWI) is one of the most recent products of this modern diagnostic era. Diffusion-weighted magnetic resonance (DW-MR) imaging provides potentially unique information on the viability of brain tissue7. It provides image contrast that is dependent on the molecular motion of water, which may be substantially altered by different diseases. Numerous studies have shown that ADCs in ischemic areas are lower by 50% or more than those of normal brain areas , and they appear as bright areas (i.e. hyper intensities) on the DWI. Studies have shown that changes in the ADC occur as early as 10 minutes following onset of ischemia. DWI shows exquisite sensitivity to ischemic stroke. Cerebral infarction (the death of neurons, glia and vessels) is caused either by insufficient inflow of blood carrying oxygen (O2) and nutrients, or reduced out flow to remove metabolic products. It basically comprises two patho-physiological processes; the first is a loss of the supply of O2 and glucose secondary to vascular occlusion, and the second is changes in cellular metabolism, with disintegration of cell membranes , cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMR O2), and cerebral metabolic rate of glucose values7,8,. Within the ischemic cerebro-vascular bed, there are two major zones of injury: the core ischemic zone and ischemic penumbra9. The penumbra is the region characterized by reversible function failure if reperfusion is restored in time and can be visualized by using advanced magnetic resonance imaging technique as combined diffusion and perfusion weighted images. Mismatches between perfusion and diffusion weighted images can estimate the ischemic penumbra. This concept immediately opens up the therapeutic time window during which restoration of flow and neuronal protection from 6 ischemic damage might prevent both immediate cell death and the recruitment of Neurons for apoptosis10. DWI helps to characterize the disease load in multiple sclerosis better than conventional methods like T1 images and FLAIR images11 . DWI helps to differentiate toxoplasmosis from lymphomas as the former shows significantly greater diffusion12. Enhancing lesions of the brain include abscesses and tumors. The center of abscesses show restricted diffusion and thus high signal intensity on DWI as compared to tumors which show low signal intensity. Thus DWI helps differentiate the two4 . Arachnoid cysts and epidermoid tumors have similar images on T1 and T2 weighted MRI images. DWI differentiates between the two as arachnoid cysts have low signal intensity as compared to epidermoid tumors4,5,6. During early brain myelination, diffusion restriction in normal white matter increases17 . When used with ADC maps, DWI can provide an objective measure of hypoxicischemic injury to the brain in neonates13. Although several studies have described the ability of DWI to help differentiate various brain tumors and to help grade gliomas, further studies are needed to define these features clearly14. Till date, the diagnostic contribution of diffusion weighted magnetic resonance imaging has been well studied in the brain where it has established and has significant role to play in the diagnosis and characterization of various diseases of the brain. It promises to provide additional information and contribute significantly in the detection and characterization of various intracranial lesions. Since there is an urgent need for the further research in this area, it is proposed to carry out this study in our institution and study the role of diffusion weighted imaging in the evaluation of various intracranial pathologies. As DW imaging improves and becomes more widespread, it is expected to play a greater role in the diagnosis of hyper acute and acute stroke and in the differentiation of stroke from other disease processes that manifest with acute neurologic deficits15. DW MR imaging will also play a greater role in the management 7 of stroke and may be helpful in the selection of patients for thrombolysis and in the evaluation of new neuro-protective agents15,16. It may prove to be valuable in the evaluation of a wide variety of other disease processes, as it will applied in our study. 8 ANNEXURE-III 6.3 OBJECTIVES OF THE STUDY: The present study is aimed to define the brain lesions in clinically suspected neurological deficits patients with the help of diffusion weighted magnetic resonance imaging and further assessment of the following 1. Evaluation of CNS lesions by Diffusion weighted imaging. 2. To study the diffusion characteristics of various CNS lesions in the form of mean ADC values and to correlate mean ADC values of various intra axial and extra axial lesions. 9 ANNEXURE-IV 7. MATERIAL AND METHODS 7.1 SOURCE OF DATA: The cases will be recruited from Al-Ameen Medical College Hospital, Bijapur and Govt. District Hospital, Bijapur. Patients referred to Department of Radiology, Al-Ameen Medical College with acute neurological deficits. INCLUSION CRITERIA. Patients referred for the MRI examination of acute neurological deficits, irrespective of age and sex. EXCLUSION CRITERIA. Patients with cardiac pacemakers , prosthetic heart valves , any metallic orthopedic implants or patients on artificial respiration. Patients with congenital lesions. Patients with bony calvarial lesions. SAMPLE SIZE: It’s a one and half year study from January 2014 to July 2015. The total number of 50 subjects will be those referred to Department of Radiology with history of acute neurological deficits. 7.2 METHOD OF COLLECTION OF DATA: 1. Details of the study protocol will be explained to the subjects. 2. Informed consent will be obtained (After clearance from ethical committee). 10 3. The study will be conducted on 50 patients referred to the department of radio diagnosis for the MRI evaluation of acute neurological deficits. 4. MRI examination of brain will be performed using SIEMENS – MAGNETOM ESSENZA 1.5 TESLA. 5. The MRI evaluation of the lesion will be done to note the size/ shape, site, margins, appearance and vascularity and relation with the adjacent structures. MRI PROTOCOL: T 1W T2W FLAIR* FOV 250 250 250 SLICE THICKNESS 5mm 5mm 5mm SPACING 30-40 30-40 30-40 TR 500-550 4000-4500 9000-9500 TE 8-15 80-90 80-120 BAND WIDTH 161Hz/Px 172 Hz/Px 190 Hz/Px 11 *FLAIR – FLUID ATTENUATED INVERSION RECOVERY. PARAMETERS OF DIFFUSION WEIGHTED IMAGING: 19-20 slices with 30-40% distance factor Slice thickness-5 mm TR- 3500-4200 TE-100-111 FOV lead -250 SCAN TIMING -51sec VOXEL SIZE-128X128 B VALUE-0-1000 s/mm2 ECHO SPACING- 1.03 ms BAND WIDTH –1056 Hz/Px CONTRAST USED: MAGNEVIST (Gadopentetate Dimeglumine Injection- 0.5 mmol/ ml solution). Dose – 0.2ml / kg body weight. STATISTICAL METHODS USED : Descriptive statistics – Frequency and percentage distribution. Graphical and diagrammatic presentation. Mean and standard deviation. Inferential statistics Chi square test for association. T test for comparison 12 ANNEXURE-V 7.3 Does the study require any investigations or interventions to be conducted on patients, humans or animals? If so please describe briefly. YES INTRAVENOUS CONTRAST ( MRI contrast agent ) NOTE: There is no animal experiment involved in the study. 13 ANNEXURE-VI 7.4. Ethical clearance from the institution: ETHICAL COMMITTEE AL-AMEEN MEDICAL COLLEGE, BIJAPUR The following study entitled “ Diffusion Weighted Magnetic Resonance Imaging with Apparent Diffusion Coefficient Maps for the evaluation of patients with Acute Neurological Deficits ” by Dr. Sameeha Khan P.G. student in Department of RadioDiagnosis belonging to 2013 batch has been cleared from ethical committee of this institution for the purpose of dissertation work. Chairman Ethical committee Al-Ameen Medical College, Bijapur 14 ANNEXURE-VII AL-AMEEN MEDICAL COLLEGE BIJAPUR 7.5: CONSENT FORM Patient’s statement I voluntarily accept admission to the Department of Radio-Diagnosis for the performance of the studies. The nature, demands and hazards involved in these studies have been fully explained to me. I understand that I may withdraw from these studies at any time for any reason. I/ guardian of the patient ( if less than 18 years) confirm that I have given my consent voluntarily to take part in the research study. I fully understand the safety issues concerning MRI and give my consent for the test. I also give consent for contrast administration if necessary, the immediate and delayed complication of contrast have been fully explained to me in my language .I consent to the release of scientific data resulting from my participation in this study to the Principal Investigator for use by him/her for scientific purposes. The principal Investigator assures my anonymity. I understand that the record of this experiment becomes part of my medical record and is protected as a confidential document. I understand that this record will only be available to physicians and investigators involved with this study. Other staff may be authorized by the Head to review the record for administrative purposes or for monitoring the quality of patient care. In the unlikely event of physical injury resulting from participation in this research, I understand that medical treatment will be available from the AMC hospital, including first aid, emergency treatment and follow–up care as needed. However, no compensation can be provided for medical care apart from the foregoing. I further understand that making such medical treatment available, or providing it, does not imply that such injury is the fault of the investigator(s). I also understand that by my participation in this study I am not waiving any of my legal rights. I understand that in the case of any problem I can contact Dr.Ramesh.V.Mankare, of the Dept of Radio-Diagnosis or any member of the Institutional Ethical Review Board, AMC Bijapur. Date: --------------------- Signature: --------------------- Witness: ------------------- Name: ---------------------- Physician’s Statement: I have carefully explained the nature, demands and foreseeable risks of the above studies to the patient. Date: -------------------- Signature: --------------------- 15 ANNEXURE – VIII LIST OF REFERENCES : 1. Maas LC, Mukherjee P. Diffusion MRI: Overview and clinical applications in neuroradiology. Applied Radiology. 2005;34:44–60. 2. Förster A, Ottomeyer C, Wolf ME, Kern R, Griebe M et al. (2010) Dynamic susceptibility contrast perfusion MRI identifies persistent vessel pathology in acute pontine stroke. Cerebrovasc Dis 29: 389-394.10.1159/000286341 PubMed: 20173322. 3. Restrepo L, Jacobs MA, Barker PB, Beauchamp NJ, Skolasky RL et al. (2005) Etiology of perfusion-diffusion magnetic resonance imaging mismatch patterns. J Neuroimaging 15: 254-260. PubMed: 15951408. 4. Mascalchi M, Filippi M, Floris R, Fonda C, Gasparotti R, Villari N. Diffusion MR imaging:clinical applications. Radiol Med 2005 march;109(3):155-197. 5. Weidauer S, Nichtweiss M, Zanella FE, Lanfermann H (2004) Assessment of paramedian thalamic infarcts: MR imaging, clinical features and prognosis. Eur Radiol 14: 1615-1626 PubMed: 15106015. 6. Steven W, Jochen G, Bettina S, Piotr W, Robert RE. acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Annals of neurology 2004;37(2):231-241. 7. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C (1991) Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 337: 1521-1526 16 8. Ronald LW, Robert AZ, Robert C, John H. Quantitative apparent diffusion coefficient measurements in term neonates for early detection of hypoxic-ischemic brain injury: initial experience. Radiology 2001;218:825-833. 9. Paciaroni M, Caso V, Agnelli G. The concept of ischemic penumbra in acute stroke and therapeutic opportunities. Eur Neurol. 2009;61(6):321-30. doi: 10.1159/000210544. 10. Manish Prasad, Shanawaz Hussain, Daniele Connolly, and Santosh Mordekar “Reversible” stroke like episodes with bilateral diffusion restriction brain magnetic resonance imaging changes J Pediatr Neurosci. 2013 May-Aug; 8(2): 173–175. 11. Tadeusz WS, Philippe D, Robert RL, Christo C, Katrijn LV, Alex M et al. Differential diagnosis of bright lesions on diffusion-weighted MR images. Radiographics 2003;23. 12. Daniel LAC, Smith JK, Mauricio C. Differentiation of toxoplasmosis and lymphomas in AIDS patients by using apparent diffusion coefficients. AJNR 2003 april;24:633637. 13. Ronald LW, Robert AZ, Robert C, John H. Quantitative apparent diffusion coefficient measurements in term neonates for early detection of hypoxic-ischemic brain injury: initial experience. Radiology 2001;218:825-833. 14. Maeda M, Kawamura Y, Tamagawa Y, et al. Intravoxel incoherent motion (IVIM) MRI in intracranial, extra-axial tumors and cysts. J Comput Assist Tomogr 1992; 16:514-518. 15. de Margerie-Mellon C, Turc G, (2013) Can DWI-ASPECTS Substitute for Lesion Volume in Acute Stroke? PubMed:24092549 16. Wey HY, Desai VR, Duong TQ. (2013) A review of current imaging methods used in stroke research. PubMed:24070268 17 17. Volkher Engelbrecht, MD , Axel Scherer, MD, Margarethe Rassek, PhD,Hans J Witsack, PhD ,Ulrich Mo¨dder, MD(2002) Diffusion-weighted MRImaging in the Brain in Children. Radiology 2002; 222:410–418 18 PROFORMA Name: Age: IP/OP No: Date: Sex: Clinical history: Past/Personal history: EXAMINATION: 1. General examination: 2. Systemic examination: 3. Local examination INVESTIGATIONS: CLINICAL DIAGNOSIS : CT SCAN / X-RAY : DW MRI FINDINGS : ADC VALUES : ADVmin−ADVmax(10-3mm2 /sec) LESION NORMAL WHITE MATTER DW MRI DIAGNOSIS: 19 ADV average (10-3mm2/sec)