THE DWI-ADC Physics and its applications in non-stroke brain pathologies Sangam Kanekar, MD Dept of Radiology Milton S Hershey Medical Center.

THE DWI-ADC Physics and its applications in non-stroke brain pathologies Sangam Kanekar, MD Dept of Radiology Milton S Hershey Medical Center

INTRODUCTION Introduction: Diffusion-weighted (DW) MR imaging has enabled us in evaluating structural and physiological states in biologic tissue by measuring the microscopic motion of the water proton. Due to its ability to diagnose cytotoxic edema it has become the main armour in the imaging of stroke, which in corelation with ADC can be diagnosed within 30 mts. Over the period of time it has been find out that there are various other pathologies which can show restricted diffusion and thus bright on DWI, due to various reasons. In this exhibit we discuss the basic physical principle behind the DWI sequence and discuss the various diffusion positive non-stroke lesion of the brain.

PHYSICS Fundamentals of DWI is based on the Brownian movement of water in tissues. What is Brownian movement ? Every molecules in any living tissue routinely undergo random (brownian) motion. Tissues with unrestricted water diffusion, the MR signal is dispersed and attenuated and thus appear low intensity on DWI. If there is restriction of water diffusion due to some reasons there is increases the signal intensity on DWI. DWI in Arachnoid cyst DWI in Abscess

PHYSICS Information regarding the brownian motion is obtained by DWI sequence. Isotropic DW is typically obtained by measuring loss of signal after a pulse sequence that consists of a series of two sequential gradient pulses added to a 90°–180° spin-echo sequence on either side of the 180° pulse. The degree signal loss after application of the second gradient pulse is related to two factors: (a) the duration and strength of the magnetic field gradients (b) (b) the diffusion coefficient of the substance (D). The degree of signal loss is represented by S/So. S= signal after application of diffusion gradients AND So= signal before use of diffusion gradients Signal attenuation is described by the formula: S/S0 = exp (- b-factor x ADC) S/S0 Ratio of Signal with diffusion gradients to Signal without diffusion gradients b-factor Attenuation factor [s/mm2], diffusion gradient dependent. ADC Apparent Diffusion Coefficient [μ m2/s], tissue dependent.

DWI SEQUENCE Single short diffusion sequence diff Gr diff Gr TE
PHYSICS DWI SEQUENCE Single short diffusion sequence 180 * 90 * diff Gr diff Gr TE Multi short diffusion sequence 180 * 90 * diff Gr diff Gr diff TE actual TE TE

PHYSICS ADC Signal attenuation in diffusion weighted imaging depends on the strength and timing of the diffusion gradients. The amount of signal attenuation is controlled by the b-factor. However, movability of the spins in biological tissue is limited by the tissue itself, and also by cell walls. Signal decay also depends on the extent of the physiological compartments. What is ADC? The observed signal decay can be used to calculate the diffusion properties, or the Apparent Diffusion Coefficient (ADC). Mobile molecules experience a substantial loss of signal that is related to the diffusion coefficient and spin-spin relaxation time (T2) of tissue, as well as the pulse sequence parameters chosen by the operator (eg, b value and excitation time). ADC is a value that describes microscopic water diffusibility in the presence of factors that restrict diffusion within tissues. In tissues, DWI probes the movement of water molecules, which occurs largely in the extracellular space. However, the movement of water molecules in the extracellular space is not entirely free, but is modified by interactions with hydrophobic cellular membranes and macromolecules. Hence, diffusion in biological tissue is often referred to as "apparent diffusion". By comparing differences in the apparent diffusion between tissues, tissue characterization becomes possible. For example, a tumour would exhibit more restricted apparent diffusion compared with a cyst because intact cellular membranes in a tumor would hinder the free movement of water molecules.

Tumors & DWI-ADC The rationale of adding DWI in the tumor evaluation is to quantify cellularity. Water diffusivity within the extracellular compartment is inversely related to the content and attenuation of the constituents of the intracellular space. Various studies have found an inverse correlation between the ADC and tumor cellularity. Higher the tumor cellularity, lower is the apparent diffusion coefficient (ADC). Decrease in the water diffusivity is due to relative reduction in extracellular space by the compact neoplastic cells. ADC values have also been shown to have inverse relation with the choline peak at MR spectroscopy and is positively correlated with tumor cell density. Note: The role of ADC in grading the cellularity of glioma appears less promising because of the limitation of ADC as a quantitative biomarker of cellularity and because of inherent and quite remarkable tissue heterogeneity associated with gliomas across different grades, within the same grade, and even within a single given tumor.

NEOPLASM INTRODUCTION: The grade of brain tumor is desicive factor in the treatment and prognosis. Though routine MR sequmces are very sensitive in diagnoses of neoplasm, grading of cellularity and identifying the perilesional presence of tumor cells have been a challenge. DWI-ADC to some extent along with perfusion may be helpful in assessing the tumor grade and cellularity, postoperative injury, peritumoral edema, and integrity of white matter tracts Based on tumor cellularity, nuclear atypia, mitotic activity, pleomorphism, vascular hyperplasia, andnecrosis gliomas have been classified into 4 grades (I–IV), where I is relatively benign (eg pilocytic astrocytoma, PXA, SGCA) while IV is highly malignant and has worse prognosis.

NEOPLASM Neoplasm Water diffusion has been found to be restricted in cellular brain tumors such as medulloblastoma, primitive neuroectodermal tumors. Restricted diffusion is believed to be due to increased cellularity, decreased extracellular space, and high nuclear-to-cytoplasmic ratio in high-grade tumors. Further in animal models it has been demonstrated that ADC increases during chemotherapy when there is a reduction in cellularity and more extracellular space and decreases back to baseline with tumor recurrence. DWI ADC +Gd Medulloblastoma restricted on DWI

NEOPLASM DWI and GLIOMAS Introduction: It is known that high grade gliomas often contains a continuum of histologic features and thus ADC values within such tumor will vary markedly, underscoring the the spectrum of glioma cellularity. It should also be well understood that tumor grade will entirely depend on the site of tumor biopsy or resection, subjecting it to sampling error. The signal intensity of gliomas on DW images is variable and a subtle hyperintensity is a commonly seen nonspecific finding. ADC values are usually in the range of 0.82 to 1.14 (x 10-3 mm2/sec). As said in the introduction ADC values cannot be used to differentiate and grade gliomas. Also DWI-ADC maps cannot distinguish neoplastic infiltration from peritumoral edema. ADC +Gd DWI

NEOPLASM DWI and GLIOMAS DW Imaging for Grading Tumors: Multiple studies have shown lower water diffusibility in high-grade gliomas than in lower grade gliomas. However there is considerable overlap between ADCs in high and low grade tumors making it difficult to use ADC as a biomarker to measure cellularity and hence grading. It remains doubtful whether tumor grade can be evaluated with enough specificity with DW imaging to be useful in a clinical context. At present DWI-ADC cannot be used to differentiate between high and low-grade gliomas or between tumor types. ADC DWI DWI Oligodendroglioma No restricted diffusion on DWI GBM No restricted diffusion on DWI

NEOPLASM DWI and definition of Tumor Margins: A number of studies have shown that ADCs in peritumoral edema are higher for metastases than for primary cerebral tumors. To date, any role for DW or diffusion-tensor imaging in the evaluation of vasogenic edema surrounding a mass remains speculative. Studies have showed considerable overlap between the ADCs of tumor and peritumoral tissues thus found that addition of DW imaging to a conventional tumor imaging protocol provided no important additional diagnostic information. +Gd ADC GBM: infiltrative tumor with extensive vasogenic edema, shows variable ADC values.

Vasogenic v/s Infiltrative edema in GBM
NEOPLASM Vasogenic v/s Infiltrative edema in GBM DWI imaging can be used to reliably distinguish vasogenic from cytotoxic edema. Whereas cytotoxic edema is characterized by restricted diffusion while vasogenic edema will show elevated diffusion. On DW MR images, vasogenic edema is hypointense to slightly hyperintense, due to T 2 shine through. Differentiation between vasogenic and infiltrative edema has been attempted with DWI, on the basis that infiltrative edema will have lesser diffusibility as compared to the vasogenic edema due to compact malignant cells. But this rule, due to heterogenity of the tumor pathology, does not hold true. Several reports have shown that ADC values are not helpful in differentiating tumor and tumor related brain edema. DWI ADC +Gd Dwi cytoxic edema from gbm DWI with extensive cytoxic-infiltrative edema from GBM

DWI & POST-OPERATIVE CHANGES
NEOPLASM DWI & POST-OPERATIVE CHANGES Restricted diffusion abnormality is not always diagnostic of acute cytotoxic edema, it can be seen in numerous intracranial diseases. Any process that results in acute intracellular swelling and subsequent decrease in the surrounding extracellular space can lead to reduced proton diffusion in the brain. Following tumor resection, acute cellular damage may be due to variety of reasons such as direct surgical trauma, retraction and vascular injury, and devascularization of tumor. Restricted diffusion in and around the site of surgery is not uncommon. Regions of reduced diffusion with contrast enhancement on a follow-up study may not always be dianostic of recurrent tumor. On long term follow-up these area has been shown to be either encephalomalacia or gliotic cavity. T2 T1 DWI Status post tumor resection DWI changes

NEOPLASM LYMPHOMA Lymphomas show iso to hypointense signal relative to gray matter on T2-weighted images and enhance homogeneously. Rim enhancement may be seen in immunocompromised patients. High signal intensity on DW images and low ADC values may favor the diagnosis of lymphoma versus glioma or metastasis. Lower ADC is likely due to higher cellularity. FLAIR +Gd DWI DWI restricted in lymphoma

NEOPLASM LYMPHOMA DWI ADC DWI +Gd ADC DWI is commonly used in diagnosis and to differentiate other tumors from lymphoma. Bright signal on DWI is proven to be due to high cellularity and corresponding decrease in the extracellular fluid and thus restriction of the fluid. ADC have been found to be decreased in lymphomas relative to other intracranial tumors such as high-grade gliomas, metastases, or meningiomas.

NEOPLASM EPENDYMOMA Ependymomas arise within IV ventricle and extend through its outlets, They are well differentiated, moderately cellular gliomas with perivascular pseudorosettes (cleared areas and radially arranged cells around blood vessels), rare mitoses with ocasional areas of necrosis, hemorrhage and calcification. The typical cellularity of ependymomas is somewhere between that of astrocytomas and medulloblastoma. Some of them may be very cellular. ADC values for ependymoma are usually between 1.05–1.33 as compared to medulloblastoma +Gd ADC DWI

Restricted diffusion in highly cellular left frontal meningioma.
NEOPLASM MENINGIOMA Meningioma are easily diagnosed by cross sectional modality. But till today differentiating and grading the various types is difficult. It was thought that atypical (WHO grade 2) and anaplastic (WHO grade 3) meningiomas exhibited lower ADC than that of benign meningioma. However, as per Kono et al study, the ADC is not indicative of the histologic subtype of meningiomas. Our study also had similar observation in few meningiomas. +Gd DWI ADC Restricted diffusion in highly cellular left frontal meningioma.

NEOPLASM MENINGIOMA +Gd DWI ADC Dwi meningioma Like other benign tumors, signal intensity of meningiomas on DWI is variable. Most benign meningiomas are isointense on DW images and ADC maps. High signal intensity on DW images and reduced ADC values suggest malignant meningioma and is again though to be due to high cellularity and corresponding decrease diffusion.

DWI+ Metastasis from adenocarcinoma of the lung
NEOPLASM METASTASIS Majority of the metastasis are iso to low signal on DWI and are high on ADC. But the signal intensity of these lesions may change depending on the histiology and composition (ie, solid tumor, degeneration, hemorrhage, and cyst). In addition SI on DWI is influenced by T2, the ADC, b value, spin attenuation, and TE used. Small cell carcinoma, adenocarcinoma may commonly show bright signal on DWI and reduced ADC. Studies have concluded that their appearance on MR imaging most likely reflected the inherent T2 effect of the tissue (the blood products calcium, mucin, and iron). DWI ADC +Gd DWI necrotic mets gd DWI+ Metastasis from adenocarcinoma of the lung 20

COLON CANCER METASTASIS
NEOPLASM METASTASIS In metastatic brain tumors or noninfiltrative primary tumors such as meningiomas, the peritumoral edema is synonymous with vasogenic edema, where there is increased extracellular water due to leakage of plasma fluid from altered tumor capillaries but no tumor cells are present. In gliomas, however, the peritumoral edema is better referred to as infiltrative edema, because it represents both vasogenic edema and infiltrating tumor cells that are behind the BBB and usually invading along the white matter tracts. +Gd ADC DWI COLON CANCER METASTASIS 21

NEOPLASM EPIDERMOID Epidermoid tumors are benign developmental tumors, with debris, keratin, water, and cholesterol. On T1 WI these tumors are mildly hypointense, while on FLAIR they show mild hyperintensity. On T2WI they are very difficult to differentiate from arachnoid cyst. T2 T2 V/S DWI DWI Fig. CP angle Epidermoid: Axial T2 & T1WI show a cystic mass in the left cerebellopontine angle causing anterior bowing of the VII-VIII nerve complex. This cyst is restricted on DWI which is very classical for epidemoid cyst. Fig: Arachnoid Cyst: Cystic intensity mass lesion is seen in the right CP angle cistern compressing & displacing the VII-VIII nerve complex anteriorly.

DWI+ Intraosseous epidermoid DWI+ petrous apex epidermoid
NEOPLASM Case 1 DWI DWI ADC Case 2 DWI+ Intraosseous epidermoid DWI+ petrous apex epidermoid EPIDERMOID CYST/ ECTODERMAL INCLUSION CYST: 90% are intra-dural in the basal cistern % of these lesions are in CPA and 17% in fourth ventricle. They are lobulated, irregular, cauliflower like mass with fronds that insinuate into cistern, and encases nerves & vessels. On CT, 95% of the time they show CSF density and fail to show any enhancement. Epidermoid cysts show restricted diffusion on DWI. Arachnoid cysts demonstrate free diffusion of water similar to that of CSF, whereas epidermoids show slower diffusion, presumably as a result of the more complex internal structure.

INFECTION INTRODUCTION:
Ring enhancing lesion, whether solitary or multifocal is always a clinical and radiological dilemma. The differential diagnosis of intracerebral necrotic tumors and cerebral abscesses is frequently impossible on conventional MR images. With DWI being routinely incorporated in the imaging of brain, differential diagnosis can be either narrowed or yet times specific diagnosis may be given. Restriction on DWI with low ADC values is seen within the pyogenic abscess cavity. Low ADC values (0.28 and mm2/s) is ascribed to the presence of intact inflammatory cells and bacteria which impede the microscopic motion of water molecules. Following surgical drainage of pus or on medications ADC shows high signal and has been shown to correlate with good therapeutic response. +Gd DWI ADC Fig: Frontal lobe abscess due to frontal sinusitis with erosion and break in the frontal bone.

INFECTION ABSCESS T2 +Gd DWI Fig: Multiple ring enhancing lesions: Differential diagnosis include abscesses, metastasis, granulomas. Multiple ring enhancing lesions are always difficult to typify as the clinical findings may be overlapping. Although highly sensitive, CT scanning is not specific. +Gd T2 DWI +CT1 Fig: Single parietal lobe abscess: Pt presented with history of seizure. Even on routine conventional MR besides abscess, similar findings may also be seen in cerebral neoplasms, cerebrovascular accidents or granulomas. However, DWI may help in giving a specific diagnosis due to central area of restricted diffusion and low ADC. The ADC values of abscess fluid are markedly lower than those of necrotic or cystic portions of tumor, which is considered to be a consequence of restricted water mobility within purulent fluid related to its high cellularity and viscosity.

ABSCESS Pretreatment Postreatment
INFECTION ABSCESS +Gd Pretreatment DWI DWI ADC Postreatment Fig: Pre and post treatment multiple brain abscesses shows change in the DWI-ADC signal following treatment. It is well documented that the treated abscess shows corresponding changes in the DWI-ADC changes. As the abscess responds to the antibiotic or therapy, restriction within the abscess decreases and ADC value increases. This definitely helps in confirming the respons to the administered therapy.

INFECTION ABSCESS +Gd DWI ADC DWI Fig: Bilateral parotid abscesses with diffuse parotid and neck lymphadenopathy in immunocompromised patient. Fig: Histologically proven left maxillary abscess shows restricted diffusion with corresponding low ADC. Low ADC values, and that the heavily impeded water mobility of pus may be related to its high cellularity and viscosity. The presence of large molecules, such as fibrinogen, also may play a key role in restricting the diffusion of protons in pus.

Subdural empyema and ventriculitis shows restricted diffusion
INFECTION VENTRICULITIS Ebisu et al (Magn Reson Imaging 1996; 14: ) performed in vitro DW imaging and ADC measurement of aspirated pus. The pus imaged in vitro showed high signal intensity and low ADC values, similar to the results of the in vivo study. Thus, they concluded that the pus structure itself is responsible for the signal changes on DWI and low ADC values. DWI changes were due to heavily impeded water mobility of pus which were in turn related to its high cellularity and viscosity. DWI DWI Subdural empyema and ventriculitis shows restricted diffusion

Subdural empyema following frontal sinusitis with DWI-ADC changes
INFECTION SUBDURAL EMPYEMA +Gd DWI ADC Subdural empyema following frontal sinusitis with DWI-ADC changes DWI lymphoma d SDE is most commonly seen in infants following purulent meningitis, while in older children, it is due to direct extension of sinusitis or otitis media into the extracranial spaces. Reactive subdural effusion (RSE), which is also seen in meningitis, is due to tears in the arachnoid membrane leading to CSF leakage in the subdural space. Differentiating SDE and RSE is critical, as RSE tends to spontaneously regress, whereas SDE generally requires aggressive intervention. Differentiation is difficult using conventional MR sequences since both are hyperintense on T2WI, and both may show peripheral enhancement on +C T1WIs. DWI is very helpful in diagnosis of SDE, since it shows restricted diffusion in empyema and not in RSE. 29

INFECTION TB & FUNGAL INFECTION +Gd DWI ADC Low ADC has also been observed in tubercular and fungal abscesses, and is considered to be the result of the presence of proteinaceous fluid and cellular infiltration in the pus. It may not be always possible to differentiate these two. Fungal cerebral abscesses show decreased diffusion, similar to pyogenic abscesses and therefore should be included in the differential diagnosis of ring-enhancing lesions with centrally restricted diffusion, especially in immunocompromised patients. Few studies also proposed that the DWI showed restricted diffusion in the projections and wall of the fungal abscess and not in the center, whereas the pyogenic and tubercular group showed restricted diffusion in the core of the cavity.

INFECTION HERPES ENCEPHALITIS T2 DWI DWI Fig Bilateral herpes encephalitis. T2WI show left temporal hyperintensity while DWI for the same patients shows restricted diffusion bilaterally suggesting bilateral herpes encephalitis. Herpes encephalitis lesions may show restricted diffusion with ADC values similar to the normal brain parenchyma, which on follow up scans these areas may demonstrate encephalomalacic change. The restricted diffusion is thought to be due to cytotoxic edema in tissue undergoing necrosis. DWI may be useful in differentiating encephalitis from infiltrative tumors. ADC values are low in herpes while tumor usually shows elevated or normal ADC range.

INFECTION a b c,d Fig. West Nile Encephalitis: (a) Axial CT at level of basal ganglia shows hyperdensity in thalami and caudate heads from petechial hemorrhages. (b-d) Axial MR images. (b)T1W image shows symmetric hyperintense signal in DGMN due to tiny hemmorhages. (c,d) DWI shows abnormal bright signal intensity in DGMN and cerebral white matter. While West Nile Encephalitis (WNE) is endemic in the Middle East, Africa and Asia, in the US, WNE is mainly seen in Northeast states. It is an arthropod-borne (mosquito) disease manifesting as encephalitis. Specific diagnosis requires serum testing with enzyme immunoassay and the plaque reduction neutralization test. MR often helps to exclude other infectious conditions, including herpes encephalitis. In the early stages of WNE, MRI may be normal. Later, involvement of the brain stem, substantia nigra and anterior horn of the spinal cord are identified. Petechial hemorrhages and DGMN involvement are also seen in later stages. DWI may show bright signal intensity either due to T2 shine through or cytotoxic damage.

CREUTZFELDT JACOB DISEASE
INFECTION CREUTZFELDT JACOB DISEASE DWI ADC sporadic CJD variant CJD CREUTZFELDT JACOB DISEASE (CJD) is a very uncommon cause of dementia and is frequently accompanied by myoclonus. There are thought to be four forms of CJD: sporadic, iatrogenic, familial and variant. Overall, the majority of cases of human prion disease are sporadic. The peak onset between 45 to 75 yrs. Pathology: is characterized by spongiform change, neuron loss and astrocytosis. In sporadic CJD, MR is quite characteristic & shows bilateral, but either asymmetric or symmetric, increased signal on T2 weighted images in the caudate and putamen. In the variant CJD the most characteristic abnormality is reported to be high intensity on T2 weighted images in the pulvinar of the thalami, termed as “ pulvinar sign”.. ADC may be significantly lower or normal or mildly elevated. This variability is related to variable amounts of spongiform change, neuronal loss, and gliosis. These changes does help in differentiating CJD from other dementias. In addition conventional MR may be normal in as many as 21% of CJD.

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
INFECTION PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) PML is a CNS infection of the immunocompromised caused by the group B human papoviruses, typically the Jacob-Creutzfeldt (JC) and Simian Virus (SV) 40 viruses. Their target is the oligodendrocyte—the cell responsible for the production of myelin. Impaired replenishment of myelin rather than “destruction” of existing myelin and this explains the long time interval between the initial HIV infection and the appearance of this disease. The attack on the oligodendrocytes tends to be patchy and progressive which is why the white matter is affected. DWI T2 FLAIR +CT1 Fig. Progressive multifocal leukoencephalopathy. T2 & FLAIR images at the level of the lateral ventricles reveal a subcortical, hyperintense signal abnormality in the right hemisphere. The lesion appears restricted to the white matter and does not exhibit mass effect. The lesion did not enhance with contrast administration. The appearance is most consistent with progressive multifocal leukoencephalopathy.

DEMYELINATING DISEASES
MULTIPLE SCLEROSIS DWI DWI The signal intensity of multiple sclerosis (MS) on DW images is variable. Most plaques demonstrate increased diffusion. Acute plaques have significantly higher ADCs than do chronic plaques due to increase in the size of the extracellular space due to edema and demyelination acutely and to axonal loss and gliosis chronically. ADC values have shown to be (1.35 x 10-3 mm2/sec) significantly higher than those for normal-appearing white matter (mean, 0.77 x 10-3 mm2/sec).

DEMYELINATING DISEASES
MULTIPLE SCLEROSIS DWI ADC +Gd Restricted diffusion seen on the DWI in acute demyelinating plaques of MS DWI Occasionally, MS lesions may show restricted diffusion with low ADC values and is thought to be due to shifts in intracellular water protons and changes in membrane permeability. The influx of inflammatory cells and associated macromolecules may also lead to restriction of water diffusion and reduction in trace ADC. Studies have also shown an increase in ADC values in normal-appearing white matter of MS.

ACUTE DISSEMINATED ENCEPHALOMYELITIS
DEMYELINATING DISEASES ACUTE DISSEMINATED ENCEPHALOMYELITIS DWI ADC +Gd Fig. ADEM Axial FLAIR & DWI-ADC images show abnormal hyperintensity in the temporal and frontal lobes at gray- white matter junction. Lesion in the left globus pallidus and splenium shows restricted diffusion. MR is highly sensitive and shows demyelinating lesions scattered in the cerebral and cerebellar white matter without mass effect. Posterior fossa involvement is more common in children. These lesions show high ADC, likely as a result of demyelination and increased extracellular water. Rarely some areas may show restricted diffusion. DWMR imaging cannot help distinguish between MS & ADEM, but can certainly differentiate these two conditions from stroke.

HEMORRHAGE Note: The appearance of hemorrhage on DW MR images is complex and depends on multiple factors, like different hemorrhagic products and the pulse sequence used. Restricted changes noted on DWI in early stages of intracranial hemorrhage are multifactorial: 1) A shrinkage of the extracellular space with clot retraction, 2) A change in the osmotic environment once blood becomes extravascular, which alters the shape of RBC, 3) the formation of the fibrin network associated with clot, 4) A conformational change of the hemoglobin macromolecule within the red blood cell. STAGE T1WI T2WI DWI ADC Hyperacute / Intracellular oxyHb Iso/ hypo Hyper Low Acute/ Intracellular deoxyHb Hypo Cannot be calculated Early acute/ Intracellular methmoHb Late subacute/ Extracellular methmoHb

HEMORRHAGE DWI OxyHb is hyperintense on DW images and has a lower ADC than does normal brain tissue; this may indicate the relative restriction of water movement inside the red blood cell. Hyperacute clot are markedly hyperintense on DWI, acute clots are markedly hypointense, early subacute clots are hypo & late subacute clots are hyperintense.

Acute/ Intracellular deoxyHb
HEMORRHAGE Acute/ Intracellular deoxyHb Early acute / Intracellular MethHb It has been demonstrated that the diffusion is reduced in hyperacute, acute, and subacute clots. Reduced ADC accounts for the marked hyperintensity on DWI scans in hyperacute and late subacute phases. Despite restricted diffusion, SI on DWI is not increased in the intervening acute and early subacute phases because of T2-induced hypointensity of clot, which dominates signal intensity on DWI (“T2 dark-through). Hemorrhage containing deoxyhemoglobin, intracellular methemoglobin, and hemosiderin are hypointense on DW images because of magnetic susceptibility effects. Because these products of hemorrhage have very low signal intensity on T2-weighted images, ADCs cannot be reliably calculated for them.

INJURY/INSULT DIFFUSE AXONAL INJURY
INTRO: Diffuse axonal injury results from shearing forces at the interface between brain structures with different density and rigidity. Extensive tissue at multiple sites may lead to profound neurologic deficits especially when trauma is coupled with hypoxia and hypotension. Though the exact mechanisms underlying the changes in diffusion associated with diffuse axonal injury are not yet fully understood, experimentally (rat study) it has been proposed that bright areas on DWI are not due to ischemic edema but rather due to neurotoxic edema causing the reduced ADCs and neuronal injury. ADC DWI DWI ADC DW diffus axo injury 41

INJURY/INSULT DIFFUSE AXONAL INJURY Schaffer et al found that among all of the sequences investigated, diffusion-weighted sequences showed the strongest correlation between lesion volume and subacute modified Rankin score at discharge. Diffusion-weighted imaging can demonstrate lesions that are not visualized with conventional MR sequences. Study also proposed that (a) the majority of diffuse axonal injuries identified were characterized by changes in water diffusivity; (b) DWI demonstrates increased contrast-to-noise ratio, compared with conventional sequences; and (c) DWI is vulnerable to susceptibility effects and, therefore, depicts many hemorrhagic lesions. Radiology October 2004 Volume 233 Number 1 Schaefer et GRE DWI ADC

INJURY/INSULT PRESS The cause of PRES is controversial. IT may be seen with eclampsia, cyclosporine/ FK-506 toxicity & systemic chemotherapy. If diagnosed early and treated patient will have no to little residual defect. However unrecognized condition can progress to ischemia, massive infarction, and even death. DWI is very reliable in distinguishing vasogenic from cytotoxic edema in the setting of cerebral ischemia. It has been hypothesized (Diego J. et al AJNR Am J Neuroradiol 23:1038–1048, June/July 2002). that 1) that the extent of regional involvement by vasogenic edema in PRES has prognostic implications and can help in identifying patients who need more aggressive treatment, 2) that severe vasogenic edema can progress to cytotoxic edema, and 3) that DWI can help in predicting the conversion to infarction and irreversible tissue damage. ADC DWI

ETHYLENE GLYCOL TOXICITY
INJURY/INSULT ETHYLENE GLYCOL TOXICITY DWI ADC DWI ADC Ethylene glycol is metabolized in the liver, and ultimately, glyoxylic acid is converted to oxalic acid, which precipitates in the presence of calcium as calcium oxalate crystals. This pathway is responsible for the metabolic acidosis and toxic symptoms. Restricted diffusion is most probably due to cytotoxic edema and presence is indicative of poor outcome.

PROFOUND HYPOXIC DAMAGE
INJURY/INSULT PROFOUND HYPOXIC DAMAGE DWI ADC DWI G Mostly seen after prolonged or acute profound hypoxic injury. Cardiac arrest in adult while nuchal cord/uterine rupture are the commonest causes in adult & infant respectively. The outcome in this patient is decided by the duration of insult to the affected brain. In profound cases there is no time for the “diving reflex”(redistribution of blood from cortex to deep gray nuclei) and therefore both the cortex as well as the deep gray matter nuclei are involved. It classically involves the posterior part of the putamen, lateral thalami and Rolandic cortex.

ACUTE WERNICKE’S ENCEPHALOPATHY
INJURY/INSULT ACUTE WERNICKE’S ENCEPHALOPATHY ADC DWI DWI Without thiamine, the Krebs and pentose phosphate cycles cannot metabolize glucose leading to cellular failure, and midline gray matter degeneration leading to WE. Pathologic changes include necrotic lesions in the mamillary bodies, periaqueductal gray matter, and walls of the III & IV ventricle. ac Microscopic exam shows pleomorphic microglia, decreased myelination, edema, swollen astrocytes, prominent blood vessels in these regions. MR findings are in parallel with pathologic changes: T2 & FLAIR show bright signal in the above regions. DWI is very rarely positive with corresponding ADC changes possibly due to microscopic changes associated with it.

METHOTREXATE TOXICITY
DWI ADC The pathophysiology of methotrexate neurotoxicity is unclear. Several mechanisms have been proposed. These include increased adenosine accumulation, homocysteine elevation and its excitatory effects on the N-methyl-D-aspartate (NMDA) receptor, and alterations of biopterin metabolism. The MR imaging findings of increased signal intensity on DWI with hypointensity on apparent diffusion coefficient (ADC) map are indicative of cytotoxic edema. This is consistent with the proposed mechanisms of a direct neurotoxic effect of methotrexate on the cell.

Conclusion Besides stroke, DWI-ADC can be sensitive and specific for various CNS pathologies. DWI-ADC provides the viability information of the brain tissue.

References 1. Diffusion-weighted MR Imaging of the Brain Radiology 2000; 217: 331. Pamela W. Schaefer, P. Ellen Grant, and R. Gilberto Gonzalez 2. Diffusion MRI: precision, accuracy and flow effects. NMR Biomed 1995; 8: Conturo TE, McKinstry RC, Aronovitz JA, Neil JJ. 3. MR imaging of high-grade cerebral gliomas: value of diffusion-weighted echoplanar pulse sequences. AJR Am J Roentgenol 1994; 162: Tien R, Felsberg G, Friedman H, Brown M, MacFall J 4. Diffusion and perfusion magnetic resonance imaging: applications to functional MRI New York, NY: Raven, Le Bihan D 5. Basic principles of diffusion-weighted imaging European Journal of Radiology 45 (2003) Roland Bammer

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THE DWI-ADC Physics and its applications in non-stroke brain pathologies Sangam Kanekar, MD Dept of Radiology Milton S Hershey Medical Center.

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