a brief of diffusion imaging in brain

1. Bright Lesions On Diffusion Weighted Imaging In Brain

3. Fick's Law J , the net amount of material diffusing across a unit cross-section perpendicular to a direction, here chosen as x , is proportional to the concentration gradient delta C /delta x (change in concentration per unit distance): In this expression, D is the diffusion coefficient and is expressed in units of m²/sec. The minus sign means that the material is transported in the direction of decreasing concentration.

5. The physical process underlying the transport of material in Fick's law is the random walk According to Einstein's law, we can expect it to end up somewhere within a sphere of radius R at time t :

7. Diffusion and Magnetic Resonance

8. Protons in a static magnetic field When protons are placed in a static magnetic field (B 0 ), they begin to precess (i.e., their magnetic vector rotates about B 0 ). Without special preparation, the protons (spins) precessing in a static magnetic field (B 0 ) do not produce signal because of lack of coherence between the individual precessions (they are all out of phase and hence have no net transverse component).

11. 90° radio frequency (RF) pulse

12. By applying a 90° RF pulse, the frequency of which matches the frequency of precession of protons, the spins can be made to be in phase and have a net transverse component, producing signal . Dephasing After the 90° RF pulse the spins will again go out of phase, mainly because of the effect of external field inhomogeneities.

14. Rephasing For static spins, The dephasing caused by external field inhomogeneities can be eliminated with a 180° pulse. This is not possible for spins undergoing diffusion because they are not static (their position fluctuates randomly because of thermal spin motion). The result is diffusion-related signal attenuation.

16. Pulsed Gradient Diffusion-weighted Imaging

17. The Stejskal-Tanner imaging sequence is used to exploit diffusion. It uses two strong gradient pulses that allow controlled diffusion weighting, according to the following equation:

18. Sensitization of a spin-echo (two-dimensional Fourier transform (2DFT) imaging sequence ) to diffusion can be easily obtained by inserting additional gradient pulses within the sequence, according to the Stejskal-Tanner scheme. By changing the amplitude G of these gradient pulses , one can modulate the degree of diffusion weighting of the echo.

19. Signal intensity on a diffusion-weighted image is defined by the formula diffusion-weighted image, still contains contributions from spin density and relaxation times T1 and T2 ; therefore, the hyperintense lesion on a diffusion-weighted image may reflect a strong T2 effect ( T2 "shine-through" effect ) instead of reduced diffusion.

20. The signal intensity on diffusion-weighted images also depends on the spin density, T1, T2, TR, and TE. To eliminate these influences and obtain pure diffusion information, we can calculate diffusion coefficient maps. A diffusion map can be calculated by combining at least two diffusion-weighted images that are differently sensitized to diffusion but remain identical with respect to the other parameters, spin density, T1, T2, TR, and TE.

21. By using, for instance, the image S 0 without diffusion weighting ( b =0) and one diffusion-weighted image ( b > 0), we can calculate a D value for each pixel with the equation A parametric image containing these data is called a diffusion map or apparent diffusion map (ADC) . The latter term emphasizes the fact that the D values obtained with this procedure depend on the experimental conditions (e.g., direction of the sensitizing gradient and diffusion time delta).

24. The Diffusion Tensor For an anisotropic diffusion process, the simple Stejskal-Tanner expression must be replaced by a more complicated one: where i and j can be any of the three spatial directions x, y, z in an orthogonal frame of reference. The b ij terms characterize the sensitizing gradients along the i and j directions, while the D ij terms are defined in terms of Fick's law for anisotropic diffusion: For an anisotropic medium, differences in concentration along, say, x can lead to a net particle flux along any of the three spatial directions x, y, z, described by D xx , D yx , D zx . Anisotropy also entails that D xx , D yy , D zz , ... will in general be different.

25. Imaging Tutorial: Differential Diagnosis of Bright Lesions on Diffusion-weighted MR Images 1 Published online November 1, 2002, 10.1148/rg.e7 Tadeusz W. Stadnik, MD, PhD, Philippe Demaerel, MD, PhD, Robert R Luypaert, PhD, Christo Chaskis, MD, Katrijn L. Van Rompaey, MD, Alex Michotte, MD and Michel J. Osteaux, MD, PhD

27. interruption of cerebral blood flow  breakdown of energy metabolism and ion exchange pumps  cytotoxic edema Acute Infarction

31. relative cerebral blood volume time-to-peak map

40. Differential Diagnosis with Venous Stroke Differential diagnosis of arterial and venous stroke may be impossible Hints for differential diagnosis: Clinical presentation (typically acute onset in arterial stroke; in venous sinus thrombosis, more insidious, frequently beginning with severe headache and/or seizures). Early hemorrhage, especially when close to the venous sinuses (unusual in acute ischemic stroke). With either or both of the above, perform MR or computed tomography (CT) venography

41. Differential Diagnosis with Cerebritis The differential diagnosis of early-stage cerebral abscesses (cerebritis) and acute infarction may be potentially problematic --capsule identification helps

46. What Is the Evolution of Acute Stroke on DW Images and ADC Maps ? DW images . —The signal intensity on DW images increases during the 1st week after symptom onset and decreases thereafter; however, it remains hyperintense for a long period (up to 72 days in the study by Lansberg et al This pattern is most likely the result of two factors : initially to reduced diffusion and thereafter to increasing T2 (T2 "shine-through"). Because the DW imaging signal remains hyperintense for a long period, it is not ideal for estimating lesion age. ADC values . —It is accepted that ADC standards decline rapidly after the onset of ischemia and subsequently increase with the "flip-flop" from dark to bright 7-10 days later This property may be used to differentiate the lesions older than 10 days from more acute ones

47. How Fast after Onset of Stroke Are Changes on DW Images and ADC Maps Detectable ? DW images and ADC maps show changes in ischemic brain tissue within hours after symptom onset, when no abnormalities are typically seen on conventional MR images

48. Conclusions The signal intensity of acute stroke on DW images increases during the 1st week after symptom onset and decreases thereafter, but signal remains hyperintense for a long period. The ADC values decline rapidly after the onset of ischemia and subsequently increase with the " flip-flop " from dark to bright 7-10 days later. This property may be used to differentiate the lesions older than 10 days from more acute ones.

49. Venous Infarction

50. Typical Presentation on DW Images and ADC Maps Diffusion findings in human venous infarction have so far been limited to conflicting case reports. The initial reports suggested increased to slightly decreased ADC values with hypo- to isointensity on DW images These findings were explained by the presence of prominent vasogenic edema associated with mild cytotoxic edema. More recently , a larger series of venous infarctions with high signal intensity on DW images and low ADC values were reported The findings were attributed to cytotoxic edema

60. Presumed Causes of Low and High Signal Intensity on DW Images The pathophysiologic mechanisms that lead to cerebral venous infarction remain controversial. Traditional models hold that retrograde venous pressure causes a breakdown of the blood-brain barrier, with leakage of fluid ( vasogenic edema ) and hemorrhage into the extracellular space. Alternatively, a pathway from venous obstruction to infarction has been proposed wherein retrograde venous pressure decreases cerebral blood flow, causing tissue damage in a manner similar to that of arterial infarction

61. In authors opinion, a coherent model should combine these two explanations. Initial event raised venous pressure  disruption of capillary tight junctions  vasogenic edema. These lesions are completely reversible, provided there is successful venous thrombolysis. Then follows cytotoxic edema  restriction of water diffusion  hyperintensity on DW images . The mechanism may be energy failure with loss of sodium-potassium pump activity, However, in contrast to arterial stroke, the "bright" lesions on DW images in venous infarction might be more susceptible to complete recovery if successfully treated.

62. Cerebral blood flow of 6 mL/100g/min will produce irreversible infarction, while the ischemic penumbra with flow values of 7-20 mL/100g/min may be salvaged after restoration of normal flow . In venous infarction, hypoperfusion develops progressively. Authors suggest it probably seldom falls under the threshold of approximately 6 mL/100g/min, since perfusion of the affected brain tissue might still be possible at lower flow rates if the blood drains through collateral pathways .The swollen cells not irreversibly damaged and therefore have a potential for recovery .

63. Tumors

64. Glioma signal intensity of gliomas on DW images is variable Occasionally the gliomas are hyperintense on DW images and show reduced ADC values (suggests reduced volume of extracellular space) or not reduced ADC values (suggests T2 "shine-through" effect)

72. Can the ADC Values Differentiate between Different Grades of Gliomas? ADC values cannot be used in individual cases to differentiate glioma types reliably (the ADCs of patients with grade II astrocytoma and glioblastoma overlap) However the combination of routine image interpretation and ADC values had a higher predictive value . (Kono et al) Clear distinction between the low-grade gliomas and the embryonal tumors (the ADC values for low-grade gliomas were 1.33 x 10 -3 mm 2 /sec ± 0.21 (range, 1.132–1.60), for nonembryonal high-grade tumors the ADC values were 1.22 x 10 -3 mm 2 /sec ± 0.09 (range, 1.128–1.303) and for the group of embryonal tumors (primitive neuroectodermal tumor, medulloblastoma, malignant teratoid-rhabdoid tumor) the ADC values were low 0.72 x 10 -3 mm 2 /sec ± 0.20 (range, 0.538–0.974).(Gauvain et al)

74. Can the DW Images and/or ADC Maps Differentiate between Glioma and Peritumoral Edema? The majority of recent studies report that DW images and/or ADC maps cannot distinguish neoplastic cell infiltration from peritumoral edema in patients with malignant glioma In 1995, Tien et al could distinguish areas of peritumoral neoplastic cell infiltration from predominantly peritumoral edema when abnormalities were located in the white matter aligned in the direction of the DW gradient. However, Recent findings do not support the hypothesis that peritumoral neoplastic cell infiltration can be depicted by means of ADCs or ADC maps

75. Metastases Typical Presentation on DW Images and ADC Maps The reported cases of metastases were isointense to slightly hyperintense on DW images, and the calculated ADC values were in the range 0.82–1.24 x 10 -3 mm 2 /sec In authors experience, the signal intensity of non necrotic components of metastases on DW images is variable (generally iso- or hypointense; occasionally hyperintense). The necrotic components of metastases show a marked signal suppression on DW MR images and increased ADC values

76. Tumor cellularity is probably a major determinant of signal intensity of solid components of cerebral metastases on DW images and on ADC values. The signal intensity of necrotic components of cerebral metastases may be related to increased free water ( usual presentation: low signal intensity on DW images, high ADC values ) and/or presence of extracellular methemoglobin and/or increased viscosity ( unusual presentation: high signal intensity on DW images, low ADC values .)

87. In authors experience, the signal intensity of nonnecrotic components of metastases on DW images is variable (generally iso- or hypointense, occasionally hyperintense). The necrotic components of cerebral metastases show a marked signal suppression on DW images and increased ADC values ( Krabbe et all).

88. Necrotic components of metastases show a marked signal suppression on DW MR images and increased ADC values

93. unusual presentation: high signal intensity on DW images, low ADC values .

99. Meningioma signal intensity of meningiomas on DW images is variable (hyper-, iso-, or hypointense) Most benign meningiomas are isointense on DW images and ADC maps Only 23%of benign meningiomas (three of 13) were slightly hyperintense in the study of Filippi et al In the same study, four malignant meningiomas had markedly increased signal intensity on DW images, decreased signal intensity on ADC maps, and low ADC values

110. Most benign meningiomas  isointense on DW images and ADC maps On average , these meningiomas had an elevated ADC value (average, 1.03 x 10 -3 mm 2 /sec ± 0.29; range, 0.62–1.80 x 10 -3 mm 2 /sec) with the exception of densely calcified or psammomatous meningiomas, which may have a low ADC (0.62 x 10 -3 mm 2 /sec). In the same study, four malignant meningiomas had markedly increased signal on DW images, hypointense signal on ADC maps, and low ADC values indicative of marked restriction to water diffusion. All these meningiomas had T2- and T1-weighted imaging characteristics suggestive of benign disease, including homogeneous signal intensity similar to that of gray matter, intense homogeneous enhancement (no cystic, necrotic, or hemorrhagic foci), smooth and distinct margins, and no evidence of brain invasion. Atypical or malignant histopathologic results were not anticipated on the basis of routine MR imaging. Tumor cellularity is probably a major determinant of ADC values of brain tumors, although probably not the only one

111. Can the DW images and ADC values differentiate between malignant and benign meningiomas? Considering the report of Filippi et al ( 34 ), DW imaging is a valuable diagnostic test in the differential diagnosis of malignant and benign meningiomas. (Four malignant or atypical meningiomas (World Health Organization [WHO] grades II and III) were extremely hyperintense on the DW images ("lightbulbs") and hypointense on the corresponding ADC maps and had markedly decreased ADC values. Thirteen benign meningiomas (WHO grade I) were hyper-, iso-, or hypointense on the DW images and on the corresponding ADC maps and had increased ADC values, with the exception of one case of a densely calcified meningioma (iso- to hypointense on DW images and iso- to hyperintense on the ADC map (ADC = 0.62 x 10 -3 mm 2 /sec. In authors experience, benign meningiomas may also show high signal intensity on DW images and reduced ADC values.

112. Tumors: Lymphoma The enhancing components of lymphoma s are generally hyperintense on DW images

118. The differential diagnosis of cerebral lymphoma , metastases, and glial tumors is frequently impossible on conventional MR images A large study is needed to confirm the potential utility of DW imaging in cases of cerebral lymphoma .

128. Tumors: Epidermoid Cyst

129. Epidermoid tumors are isointense to slightly hyperintense relative to cerebrospinal fluid on T1-, T2-, and proton density-weighted images It is difficult to discern the exact extension of an Epidermoid tumor with only T1-, T2-, or proton density-weighted imaging. On DW images, Epidermoid tumors show high signal intensity and are easily differentiated from cerebrospinal fluid or arachnoid cysts Constructive interference in the steady state (CISS) and FLAIR sequences also depict Epidermoid tumors in the subarachnoid spaces better than conventional SE images

130. The reported mean ADC value of Epidermoid tumors was 1.197 x 10 -3 mm 2 /sec. In authors experience, the ADC values of Epidermoid cyst and gray and white matter are similar. Therefore, the high signal intensity of Epidermoid cysts on DW images suggests the T2 shine-through effect.

135. reported mean ADC value of Epidermoid tumors was 1.197 x 10 -3 mm 2 /sec . ADC values of Epidermoid cyst and of gray and white matter are similar. Therefore, the high signal intensity of epidermoid tumors on DW images suggests the T2 shine-through effect.

137. Arachnoid cyst

142. Inflammation: Abscess

147. Differential Diagnosis of Abscess and Acute Ischemic Stroke During the initial cerebritis stage (an ill-defined subcortical hyperintense zone on T2-weighted images associated with poorly delineated enhancing areas within the iso- to mildly hypointense edematous region on enhanced T1-weighted images) , the differential diagnosis of abscess and acute ischemic stroke may be difficult. Hints for differential diagnosis: Clinical presentation (typically acute onset in ischemic stroke). Parenchymal contrast material uptake ( unusual in subacute ischemic stroke ). ADC values (reported ADC values of cerebral abscesses are ±50% lower than those of ischemic stroke after 8 hours).

148. Differential Diagnosis of Abscess and Cystic or Necrotic Tumors The differential diagnosis of intracerebral necrotic tumors and cerebral abscesses is frequently impossible on conventional MR images. The DW image is a diagnostic clue in cases of a cerebral ring-enhancing mass. Pyogenic brain abscess has been reported to have markedly increased signal intensity on DW images and markedly decreased signal intensity on ADC maps, while the opposite happens in necrotic tumors . However, Tung et al recently reported two metastases, both squamous cell carcinomas, and one case of radiation necrosis with markedly increased signal intensity on DW images and a low ADC value .They speculate that restricted diffusion in these cases was due to sterile liquefaction necrosis.

153. Hints for differential diagnosis: Presentation on DW images and ADC values. The cystic or necrotic components of tumors show marked signal suppression on DW images, similar to that of the CSF, and the reported ADC values are in the range of 2.2 x 10 -3 mm 2 /sec ± 0.9 and 1.65–2.62 x 10 -3 mm 2 /sec .

154. Conclusions DW imaging and ADC maps are useful in the differential diagnosis of ring-enhancing cerebral masses . The presence of restriction on DW images and low ADC values strongly suggest the presence of pus and abscess. The differential diagnosis includes acute infarction, which also shows hyperintensity on DW images and reduced ADC values. Nevertheless, the ring enhancement in acute ischemic stroke is unusual, and ADC values are higher after 8 hours . The ring-enhancing mass with no restriction on DW images and an increase in ADC values suggest necrotic tumor, most frequently cerebral glioma or metastasis . For these reasons, DW imaging and calculations of ADC values should be performed in all cases of ring-enhancing cerebral masses.

155. Inflammation: Granuloma

156. Typical Presentation on DW Images and ADC Maps In author’s experience, the increased signal intensity on DW images and a low ADC value are common in inflammatory granulomas

162. Differential Diagnosis of Granulomas and Nodular Cerebral Metastases The differential diagnosis of intracerebral nodular metastases and cerebral granulomas is frequently not possible on either conventional MR images or DW images. Nodular metastases frequently show high signal intensity on DW images and low ADC values (related to high cellularity and/or hemorrhage)

173. Conclusions Experience with diffusion findings in cerebral granulomas is limited . In author’s experience, the differential diagnosis of intracerebral nodular metastases and cerebral granulomas is frequently not possible on either conventional MR images or DW images.

174. Inflammation: Encephalitis

175. Herpes encephalitis lesions are characterized by marked hyperintensity on DW images and reduced ADC values . On follow-up T1- and T2-weighted MR images, these areas demonstrate encephalomalacic change .

180. Differential Diagnosis Hints for differential diagnosis herpes encephalitis versus infiltrative temporal lobe glial tumors: If confirmed, the hyper intensity on DW images and reduced ADC values favor the diagnosis of herpes encephalitis . Biological tests (polymerase chain reaction test). The differential diagnosis between acute ischemic stroke and herpes encephalitis may be problematic on DW images. Hints for differential diagnosis herpes encephalitis versus ischemic stroke: Clinical presentation (acute onset in ischemic stroke, more progressive in herpes encephalitis). Biological tests (polymerase chain reaction test). Initial reports suggest that herpes encephalitis lesions are characterized by marked hyper intensity on DW images and reduced ADC values (48%–66%of those of normal brain parenchyma)

181. Hemorrhage

182. High signal intensity on DW images is reported in hyperacute (intracellular oxyhemoglobin) and late subacute (extracellular methemoglobin) stages of hemorrhage . The ADC values  decreased or normal in hyperacute stages and increased in the late subacute stage.

192. Differential Diagnosis with Hyperacute Ischemic Stroke The differential diagnosis of hyperacute ischemic stroke and hemorrhage may be impossible on DW images and ADC maps alone. Conjoint use of DW images and ADC maps with T2-weighted SE or T2*-weighted gradient-echo and/or T2-weighted echo-planar images, especially during the therapeutic window for thrombolysis (up to 3 hours after onset), is mandatory in differentiating hyperacute stroke from hyperacute hemorrhage. Hints for differential diagnosis: hyperacute ischemic stroke the T2-weighted SE and T2*-weighted gradient-echo findings are normal. hyperacute hemorrhage, heterogeneous hyperintensity with a hypointense rim is seen on T2-weighted SE and T2*-weighted gradient-echo images.

193. Conclusions recognition of early intracranial hemorrhage, specifically on MR images, has become important because the primary assessment of patients with early stroke is moving toward MR imaging and away from CT scanning . As DW imaging becomes integrated into the initial emergent evaluation of patients with acute stroke, it becomes paramount to understand the manifestations of intracranial hemorrhage on DW MR imaging specifically. The differential diagnosis of hyperacute ischemic stroke and hemorrhage may be impossible on DW images and ADC maps alone.

194. Multiple Sclerosis

195. In author’s experience, the signal intensity of multiple sclerosis (MS) on DW images is variable (hyper-, iso-, or hypointense) Gass et al reported that enhancing lesions were restricted relative to white matter on DW images , while chronic lesions were not . Most studies focus on ADC values in MS . These studies show an increase in ADC values in MS lesions and perhaps also in the ADC values of normal-appearing white matter of MS patients . Therefore, we can hypothesize that the restriction in MS lesions on DW images results from the T2 shine-through effect.

202. Conclusions In author’s experience, the signal intensity of MS lesions on DW images is variable (hyper-, iso-, or hypointense). The majority of studies have showed increases in ADC values in MS lesions and perhaps in the ADC values of normal-appearing white matter of MS patients . Therefore, we can hypothesize that the increased intensity of MS lesions on DW images is due to the T2 shine-through effect. Occasionally, the high-intensity plaques on DW images (especially homogeneously enhancing lesions) may show reduced ADC values. Perhaps the subset of homogeneously enhancing lesions with a low trace ADC represents a very early enhancing lesion with marked inflammation and no substantial demyelination .

203. Creutzfeld-Jakob Disease

204. The reported cases of sporadic Creutzfeld-Jakob disease (CJD) showed high signal intensities in the basal ganglia (putamen and caudate nucleus) and in the cortex on DW images . The high signal intensities in the basal ganglia are also prevalent on T2-weighted and FLAIR images. The cortical hyperintensities are usually not visualized on T2-weighted and FLAIR images (advantage of DW imaging)

208. Hints for differential diagnosis: Clinical presentation (typically acute onset in ischemic stroke). ADC values (decreased in acute stroke, approximately similar to those of white matter in CJD). Differential Diagnosis of CJD and Acute Ischemic Stroke Differential Diagnosis of CJD, Progressive Multifocal Leukoencephalopathy, and Subacute Sclerosing Panencephalitis (SSPE) Hints for differential diagnosis: On T2-weighetd and FLAIR images, PML and SSPE are associated with white matter lesions, while CJD is not. The high-signal-intensity cortical lesions on DW images may be also a hallmark of CJD.

210. The typical presentation of sporadic CJD on MR images includes high signal intensities in the basal ganglia (putamen, caudate nucleus) and cortex. DW imaging is more sensitive than T2- or proton density-weighted imaging in detecting cortical abnormalities. The DW images may provide a diagnostic clue in early detection of CJD

211. Other Bright Lesions on DW Images "When you’ve got a new hammer, everything looks like a nail.“ Michael Brant-Zawadzki

212. Sustained Seizure Activity Eclampsia neuroradiologic hallmarks of eclampsia are reversible abnormalities that appear hypoattenuating on CT studies and hyperintense on T2-weighted MR images, in a subcortical, predominantly parietal and occipital distribution transient increase in signal intensity and swelling in the cortical gray matter, subcortical white matter, or hippocampus on periictal T2-weighted images ,and on DW images .The ADC values were reduced by 6%–28%compared with either the normal structure opposite the lesion Central Pontine Myelinolysis patients with central pontine myelinolysis were studied with DW imaging 1 week after onset of tetraplegia. In both patients, affected white matter showed hyperintensity on DW images, associated with a decrease in ADC values

213. Thank you. Laxmishankar Dixit…