DIFFUSION & PERFUSION MRI IMAGING Dr. Wael Darwish

DIFFUSION MRI IMAGING

- History - The feasibility of diffusion images was demonstrated in the middle 1980s Demonstration on clinical studies is more recent ; it corresponds with the availability of EPI on MR system A single shot EPI sequence can freeze the macroscopic pulsating motion of the brain or motion of the patient’s head

Diffusion Weighted Image Core of infarct = irreversible damage Surrounding ischemic area  may be salvaged DWI: open a window of opportunity during which ttt is beneficial DWI: images the random motion of water molecules as they diffuse through the extra-cellular space Regions of high mobility “rapid diffusion”  dark Regions of low mobility “slow diffusion”  bright Difficulty: DWI is highly sensitive to all of types of motion (blood flow, pulsatility, bulk patient motion,……).

- Diffusion contrast - Diffusion gradients sensitize MR Image to motion of water molecules More motion = Darker image Freely Diffusing Water = Dark Restricted Diffusion = Bright

- Principles - Velocities and methods of measurement

- Principles - About the b factor b is a value that include all gradients effect (imaging gradients + diffusion gradients) The b value can be regarded as analogous to the TE for the T2 weighting

Medium High Low “b = 500” “b = 1000” “b = 5”

- Principles - About ADC The ADC value does not depend on the field strength of the magnet or on the pulse sequence used (which is different for T1 or T2) The ADC obtained at different times in a given patient or in different patients or in different hospitals can be compared

- Principles - Isotropic and Anisotropic diffusion Diffusion is a three dimensional process, but molecular mobility may not be the same in all directions In brain white matter, diffusion’s value depends on the orientation of the myelin fiber tracts and on the gradient direction*

Anisotropic diffusion : Individual direction weighted X Diffusion - Weighting Y Diffusion - Weighting Z Diffusion - Weighting

Isotropic diffusion - + x / Isotropic Diffusion- Individual Diffusion Weighted Image Individual Diffusion Directions Mathematical Combination (Sorensen et al., MGH) - + x /

Diffusion weighted image

Short TE DWI gives more SNR Characteristics of diffusion’s contrast Short TE DWI gives more SNR TE=100ms SR 120 b = 1000 s/mm 2 TE=75ms SR150

Characteristics of diffusion’s contrast Higher b value increases sensitivity MS Higher CNR helps distinguish active lesions Stroke Higher CNR Vasogenic edema Cytotoxic Edema Tumor Vasogenic edema b = 1000 b= 3000

Mathematical Processing Diffusion-weighted ADC map

Mathematical Processing Diffusion-weighted ADC map Exponential ADC

Diffusion Imaging Processing Exponential ADC (ratio of Isotropic DWI/T2) eliminates T2 shine through artifacts and may distinguish subacute from acute stroke

Arachnoid Cyst b=0 b=1000 ADC eADC

Clinical Application

MR Images of 60-Year-Old Man with Glioblastoma Multiforme . 2. Figures 1, 2. On (1) T2-weighted fast spin-echo and (2) contrast-enhanced T1-weighted spin-echo images, the differential diagnosis between glioblastoma and abscess is impossible.

3. 4. . central hypointensity on diffusion-weighted image and hyperintensity on ADC map, consistent with the diagnosis of tumor.

MR Images of 57-Year-Old Woman with Cerebral Metastasis 5. 6.

7. 8. central hypointensity on diffusion-weighted image and hyperintensity on ADC map, consistent with the diagnosis of tumor.

MR Images of 70-Year-Old Man with History of Recent Vertigo and Disequilibrium 1. 2.

3. 4. A brain abscess with Streptococcus anginosus was found at surgery.

5. 6. MR Images of 57-Year-Old Woman with Cerebral Metastasis the differential diagnosis between metastasis and abscess is impossible.

7. 8. Central hypointensity is seen on the diffusion-weighted image and hyperintensity on the ADC map, consistent with the diagnosis of tumor.

APPLICATIONS SPINE

BENIGN VERSUS MALIGNANT FRACTURE

This finding indicates that the lack of signal reduction in malignant vertebral fractures is caused by tumor cell infiltration Different diffusion effect is caused by more restriction or hindrance in densely packed tumor cells compared with more mobile water in extracellular volume fractions in fractures

diffusion-weighted spin-echo sequences could differentiate benign fracture edemas and fractures caused by tumor infiltration due to higher restriction of water mobility in tumor cells.

T2-weighted MR image shows ovoid hypointense mass in spinal canal.

T1-weighted sagittal MR image after infusion of gadolinium contrast material shows diffuse signal enhancement of mass.

T1-weighted transverse MR image after infusion of contrast material shows extent of tumor in spinal canal and C4-C5 neural foramen

Diffusion-weighted sagittal MR image using peripheral pulse gating and navigator correction shows signal intensity of mass (open arrows) to be intermediate, less than that of brainstem (large solid arrow) and greater than that of vertebral bodies (small solid arrows).

ADC map shows mass (arrows) as structure of intermediate intensity. MENINGIOMA

In that study, tumors with high cellularity had low mean ADC values, and tumors with low cellularity had high mean ADC values. In addition, the relatively high ADC value seen in our patient corresponded to a low degree of cellularity, such as has been reported in cerebral gliomas.

Perfusion imaging Definitions Principles Some more definitions Perfusion technique Applications Future

Definitions Perfusion is refer to the delivery of oxygen and nutrients to the cells via capillaries Perfusion is identified with blood flow which is measured in milliliters per minute per 100 g of tissue

Principles After injection of a contrast agent In normal brain, the paramagnetic contrast agent remains enclosed within the cerebral vasculature because of the blood brain barrier The difference in magnetic susceptibility between the tissue and the blood results in local magnetic field finally to large signal loss

Some more Definitions rCBF “ the rate of supply of Gd chelate to a specified mass ” ( ml / 100g / min) rCBV - “ the volume of distribution of the Gd chelate during its first passage through the brain ” ( % or ml / 100g ) MTT - “ the average time required for any given particle to pass through the tissue, following an idealised input function ” (min or s) MTT = rCBV / rCBF

Passage of Gd. can be followed by the changes in the relaxation rates concentration of local contrast. Linear relation bet. concentration and rates of signal changes can be expressed as curve. Tissue contrast concentration time curve can be used to determine tissue micro vascularity, volume and flow.

At each voxel we observe : slice n ~ ‘mean transit time’ time Integral:= cerebral blood volume intensity time

Principles Each one of these effects is linearly proportional to the concentration of the paramagnetic agent To date, this technique results in non-quantitative perfusion parameters (like rCBV,rCBF or MTT) because of the ignorance of the arterial input function

Principles - + x / Dynamic Susceptibility Contrast Imaging First Pass Extract time-intensity curves Perform mathematical manipulation Generate functional maps + + NEI - + x / MTE Negative Enhancement Integral Map(NEI) Qualitative rCBV map Mean Time to Enhance (MTE)Map Ischaemic Penumbra First Pass Contrast bolus

Hemodynamics Bl. volume Bl. flow Dynamic MR perfusion Hemodynamics Bl. volume Bl. flow Aim 1. Diagnosis 2. Monitoring management 3. Understanding intracranial lesions

rCBV rCBV, processed with “Negative Enhancement Integral”(NEI) is related to area under curve

MTT MTT is related to the time to peak and to the width of the peak ; it is processed with “Mean Time to Enhance“(MTE)

Cerebral blood perfusion by bolus tracking Requires very high speed imaging power injector - Gadolium 5ml/sec Procedure : 1 - Start Imaging 2 - Inject Contrast* 3 - Continue Imaging 10 slices - 50 images of each slice - TOTAL time 1:34 min * Push Gadolinium with 20 cc of saline flush

Applications of Perfusion MRI Neurology Gerontology Neuro-oncology Neurophysiology Neuropharmacology

Perfusion Imaging: Findings in Infarction Stroke Perfusion Imaging: Findings in Infarction CBV regional perfusion deficit compensatory increased volume MTT regional prolongation of transit time

Head Trauma T2 image showing bifrontal volume loss FLAIR image showing bifrontal gliosis and encephalomalacia

Head trauma:Hypo-perfusion rCBV MAP Tc-HMPAO SPECT Hypo-perfusion

E.g. 1 : Left hemisphere stroke, 4.5 hrs after onset of symptoms 3D-TOF Vascular FSE-T2W FSE-FLAIR

Same patient with DWI and FLAIR EPI FLAIR 4.5 hrs 24 hrs Diffusion imaging shows lesion early. b=0 b=800 FLAIR shows enhanced changes after 24 hrs. 4.5 hrs

Isotropic diffusion image Apparent diffusion coefficient ADC ADC map Isotropic diffusion image b=800

Contrast enhanced perfusion imaging 24 slices 3 seconds/acquisition Time/intensity graph

Mean Time To Enhance delayed compensatory hyperperfusion delayed hypoperfusion

Diffusion Coefficient* EPI Diffusion and Perfusion mapping MTT Mean Time To Enhance CBV Negative Enhancement Integral ADC Diffusion Coefficient* EPI Diffusion EPI Perfusion

Findings with Perfusion Imaging for Infarction Changes seen almost immediately after the induction of ischemia more sensitive than conventional MRI Perfusion findings often more extensive than those on DW-EPI in early stroke more accurately reflects the amount of tissue under ischemic conditions in the hyperacute period than DW EPI Abnormal results correlate with an increased risk of stroke PerfEPI - DWEPI = tissue at risk

Findings with Perfusion imaging for Gerontology Alzheimer’s disease FDG PET marked temporo-parietal hypometabolism Tc-HMPAO SPECT marked temporo-parietal hypoperfusion DSC MRI correlates well with SPECT

Findings with Perfusion imaging for Neurophysiology and pharmacology Traumatic brain injury focal rCBV deficits that correlate with cognitive impairment Schizophrenia decreased frontal lobe rCBV HIV/ AIDS multiple discrete foci of decreased CBV Polysubstance abuse New Jersey Neuroscience Institute

Findings with Perfusion imaging for Neuro-oncology Critical imaging to BBBB imaging of neoplasm many tumors have high rCBV regions of increased rCBV correlate with areas of active tumor. heterogeneous patterns of perfusion suggest high grade radiation necrosis typically demonstrates low rCBV Lesion characterization may be possible meningiomas have very high CBV in contrast to schwannomas New Jersey Neuroscience Institute

Intracranial neoplasm N.B angiogenesis usually = aggressiveness Dynamic MR perfusion Clinical applications:- Intracranial neoplasm N.B angiogenesis usually = aggressiveness Exceptions:- 1. Meningioma 2.Choroid plexus papilloma 1.Glioma Grading Biopsy D.D recurrence from radiation necrosis

2.Metastasis Can differentiate solitary metastasis from 1ry brain neoplasm (glioma) by measuring the peritumoral relative blood volume. 3.1ry cerebral lymphoma Can help in differentiating lymphoma from glioma as lymphoma is much less vascular

4. Meningioma Hypervascular Extra axial Has leaky and permeable capillaries causing no recovery of T2* signal to basline. 5. Tumor mimicking lesions e.g. cerebral infections tumefactive demyelinating lesions less commonly infarcts

6.Tumefactive demyelinating lesions No neo-vascularization in demyelinating lesions To conclude MR perfusion should be included in routine evaluation of brain tumor as it improve diagnostic accuracy.

Neuro-oncology rCBV maps low rCBV in tumour infers low grade glioma

Eg2 Diffused tumor: Abnormal capillary density Glioblastoma multiform Hyper perfusion Excised region Before surgery MTSE shows blood brain / barrier breakdown (bbbb) After surgery rCBV map shows diffuse disease in right frontal lobe

Eg3 tumor vs.radiation necrosis CBV Conventional T2 Non specific changes Recurrent Tumor