Formulation Development, Characterization and In-vitro Evaluation of Tamoxifen Loaded Liposomes

Background: The study was aimed to prepare and evaluate tamoxifen loaded controlled release liposomes to reduce the side effects of tamoxifen during cancer treatment. Methods: Different tamoxifen loaded liposomes were prepared by modified ether injection (MEIM) and thin film hydration method (TFHM) under prescribed conditions. The prepared liposomes were characterized by using optical microscopy, evaluating encapsulation efficiency, in-vitro and ex-vivo diffusion studies by using dialysis membrane and chicken intestinal sac respectively.Results: The data revealed that all of the liposomes were spherical in shape and stable under three physical conditions i.e. 4, 25 and 37 ± 2°C temperatures and 60 ±5% relative humidity. Additionally most of the liposomes followed zero order and class II release kinetics. It was also observed that with the increase of phospholipids and cholesterol, entrapment efficiency of liposome vesicles increased thus giving a controlled release drug delivery system but further increase reduced this efficiency at a certain level.Conclusion: The formulated control release liposomes might be a good drug delivery system for target oriented drug delivery with minimum side effects of tamoxifen during cancer treatment

Medium Molecular Weight Chitosan as a Carrier for Delivery of Lincomycin Hydrochloride from Intra-pocket Dental Film: Design, Development, in vitro and ex vivo Characterization.

The purpose of investigation is to find out the potential of Medium Molecular Weight Chitosan (MMWCH) loaded with Lincomycin Hydrochloride (LNC) having pKa 7.6 and log p value 0.20 for treatment of periodontitis and gingivitis, prepared by using solvent casting technology in form of intra pocket dental film. Four sets of formulation were prepared and each set comprises of four formulations each. The formulations were evaluated for drug content uniformity, weight uniformity, thickness of patch, surface pH, moisture loss, swelling index, water vapor transmission rate, static in vitro release studies using diffusion cell, ex vivo flux study using diffusion cell by help of excised gum lining of goat, release kinetics and Akaike Information Criteria; goodness of fit (AIC) value determination. Excipient drug interaction was carried out by using Fourier Transform Infrared spectroscopy (FTIR), and by Thermo gravimetric Analysis (TGA)/Differential thermal analysis (DTA)/Derivative thermo gravimetric analysis (DTG) and this suggests that there is no drug excipient interaction occurs. The drug release studies show the sustained release without any burst effect for consecutive 5 days. Formulation R1, R2, R7, R8, R9, R10, R13 and R14 and follows the zero order release pattern and formulation R3, R4, R5, R6, R11, R12, R15 and R16 follows the Higuchi model because they have lower AIC value and higher r2 value. Formulation ER17, ER18, ER19 and ER20 is having the average flux of 1.0, 1.48, 1.35 and 1.45 mg/cm2 hr-1 respectively, and when compared statistically student’s paired t-test these all formulations are significantly different from each other.

Proniosomal Gel of Tretinoin for the Treatment of Acne Vulgaris.

The objective of the present study was to formulate and evaluate Tretinoin proniosomal gel and to carry out comparative skin irritation study with conventional Tretinoin solution and Tretinoin conventional gel. Topical Tretinoin (0.25%, 0.05%) has been a reliable treatment of acne vulgaris since 30 years but its major drawback is that it causes skin irritation on the applied area. The proniosomal dispersion was prepared using different grades of non-ionic surfactants and cholesterol in different ratios along with Tretinoin. The scanning electron microscopy revealed that the proniosome vesicles were of LUV type and spherical shape. The proniosome vesicles prepared with SPAN 60, 40 and cholesterol in formulation PN9 showed maximum entrapment efficiency (76.77±1.54) .The prepared proniosome vesicles were incorporated into Carbopol gel (1%) base to prepare Tretinoin proniosomal gel. The stability study was carried out at different accelerated and non-accelerated conditions. The In-vitro diffusion study carried out using sigma dialysis membrane showed sustained release pattern of Tretinoin from proniosomal gel formulation. The comparative skin irritation study carried out on 18 healthy Wistar Rats of either sex showed remarkable decrease in signs of skin irritation caused by Tretinoin.

Apparent Diffusion Coefficient Value of Diffusion-Weighted Imaging for Hepatocellular Carcinoma: Correlation with the Histologic Differentiation and the Expression of Vascular Endothelial Growth Factor

OBJECTIVE: To evaluate whether the histopathological differentiation and the expression of vascular endothelial growth factor (VEGF) of hepatocellular carcinoma (HCC) do show correlation with the apparent diffusion coefficient (ADC) value on diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Twenty-seven HCCs from 27 patients who had undergone preoperative liver MRI (1.5T) and surgical resection were retrospectively reviewed. DWI was obtained with a single-shot, echo-planar imaging sequence in the axial plane (b values: 0 and 1,000 sec/mm2). On DWIs, the ADC value of the HCCs was measured by one radiologist, who was kept 'blinded' to the histological findings. Histopathologically, the differentiation was classified into well (n = 9), moderate (n = 9) and poor (n = 9). The expression of VEGF was semiquantitatively graded as grade 0 (n = 8), grade 1 (n = 9) and grade 2 (n = 10). We analyzed whether the histopathological differentiation and the expression of VEGF of the HCC showed correlation with the ADC value on DWI. RESULTS: The mean ADC value of the poorly-differentiated HCCs (0.9 +/- 0.13x10(-3) mm2/s) was lower than those of the well-differentiated HCCs (1.2 +/- 0.22x10(-3) mm2/s) (p = 0.031) and moderately-differentiated HCCs (1.1 +/- 0.01x10(-3) mm2/s) (p = 0.013). There was a significant correlation between the differentiation and the ADC value of the HCCs (r = -0.51, p = 0.012). The mean ADC of the HCCs with a VEGF expression grade of 0, 1 and 2 was 1.1 +/- 0.17, 1.1 +/- 0.21 and 1.1 +/- 0.18x10(-3) mm2/s, respectively. The VEGF expression did not show correlation with the ADC value of the HCCs (r = 0.07, p = 0.74). CONCLUSION: The histopathological differentiation of HCC shows inverse correlation with the ADC value. Therefore, DWI with ADC measurement may be a valuable tool for noninvasively predicting the differentiation of HCC.

Bilateral Medial Medullary Infarction Demonstrated by Diffusion-Weighted Imaging: Case Report / 영남의대학술지

A 78-year-old woman presented with weakness of the extremities, dysarthria, dizziness, and sensory impairment. Magnetic resonance imaging showed acute bilateral medial medullary infarction. Contrast enhanced magnetic resonance angiography demonstrated stenosis or occlusion of both intracranial vertebral arteries. We present a rare case of bilateral medullary infarction seen on diffusion-weighted imaging.

Diffusion-Weighted MR Imaging of Unusual White Matter Lesion in a Patient with Menkes Disease

We report here on the diffusion-weighted imaging of unusual white matter lesions in a case of Menkes disease. On the initial MR imaging, the white matter lesions were localized in the deep periventricular white matter in the absence of diffuse cortical atrophy. The lesion showed diffuse high signal on the diffusion-weighted images and diffuse progression and persistent hyperintensity on the follow up imaging. Our case suggests that the white matter lesion may precede diffuse cortical atrophy in a patient with Menkes disease.

Diffusion-Weighted MR Images for Hyperacute Cerebral Infarction: Design of a Quick Volume Estimation Method for Hyperintensities

PURPOSE: To design a reliable and quick lesion volume estimation method for hyperintensities on diffusion-weighted images (DWI) for the evaluation of hyperacute stroke. MATERIALS AND METHODS: Twenty patients with obvious high signal lesions seen on DWI in the middle cerebral artery territory due to acute ischemia were enrolled to evaluate the performance of four tentatively designed semi-quantitative methods: the 25-area method, the 20-area method, the 10-area method, and the modified 10-area method. Two radiologists performed the volume analyses using these methods. Intraclass correlation coefficients were calculated to compare the correlation between the reference values and the measured values and to evaluate the interobserver agreement of each method. RESULTS: For the correlation between the measured value and the reference value, the performance of the modified 10-area method was the most powerful, with a value of 0.8981 and 0.8090 for observer 1 and 2, respectively. The interobserver agreement was satisfactory for both the 25-area method and the modified 10-area method, with a value of 0.9212 (95% CI: 0.8123-0.9681) and 0.9063 (95% CI: 0.7790-0.9618), respectively. CONCLUSION: The performance of the modified 10-area method was satisfactory for both lesion volume estimation and interobserver correlation in the evaluation of an acute cerebral infarction by the use of DWI.

Assessment of Tissue Viability in Hyperacute Infarction with Using the Diffusion- and Perfusion-weighted Images

PURPOSE: The presence of a perfusion-diffusion mismatch is a useful indicator for predicting the progression of acute cerebral infarction. However, not all the area of the perfusion-diffusion mismatch progresses to infarction and a large proportion survives with hypoperfusion. The purpose of this study was to assess 1) whether tissue viability can be predicted using quantitative perfusion values and 2) whether there is correlation between the perfusion value and the time that elapsed after the onset of symptoms. MATERIALS AND METHODS: Twenty-two patients with acute infarction in the middle cerebral artery territory within 12 hours after symptom onset were included in this study. We excluded those patients in whom thrombolysis was attempted or the lesion volume was less than 5 mL. Patients without perfusion-diffusion mismatch on the mean transit time (MTT) map were also excluded. We categorized the ischemic lesions into 3 areas: 1) the initial infarction, 2) the area that progressed to infarction, and 3) the hypoperfused but surviving area, based on the initial and follow up diffusion-weighted images and initial mean transit time (MTT) map. We obtained the relative cerebral blood volume (rCBV), the cerebral blood flow (rCBF) and the MTT in each area by comparing to the contralateral normal area. Statistical analysis was performed using one-way ANOVA to test whether there was a difference in perfusion values between each area. The threshold value was calculated between areas 2 and 3 using the receiver operating characteristics curve. We analyzed the correlation between the perfusion values of each area and the time that elapsed after the inset of symptoms. RESULTS: The perfusion values among each region were significantly different on the rCBV, rCBF and MTT maps. Between regions 2 and 3, the rCBV and rCBF maps showed a significant difference (Bonferroni post hoc analysis), but in case of rCBV, the mean perfusion values in each region approached to the normal level and it was difficult to differentiate between the two regions on the rCBV map. The rCBF in the regions 1, 2 and 3 was 0.40, 0.64, and 0.84, respectively. The difference of the threshold values of the rCBF between regions 2 and 3 was 0.75. There was no significant correlation between the time that elapsed after symptom onset and the perfusion values of each region on the rCBV, rCBF and MTT map. CONCLUSION: The perfusion values between the area of the initial infarction, the area that progressed to infarction and the hypoperfused but surviving area showed significant differences. The rCBF was the most useful parameter in differentiating between areas that progressed to infarction and the surviving areas. Quantitative measurement of the perfusion values may have a role in selecting the candidates for thrombolysis after they have suffered hyperacute stroke.

PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) and EPI Diffusion-weighted MR Imaging at 3.0T: Pontine Magnetic Susceptibility Artifacts Depend on Pneumatization of the Sphenoid Sinus

PURPOSE: In the case of well pneumatized sphenoid sinus, magnetic susceptibility artifact can be visualized at the brainstem and especially at the pons on echo-planar imaging (EPI) diffusion-weighted imaging. Fast spin-echo periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) is a novel imaging method that can reduce these artifacts. In 3.0T MR, we first evaluate the degree of the relationship of pneumatization of the sphenoid sinus with the occurrence of magnetic susceptibility artifacts (MSA) on the echo planar imaging (EPI) diffusion-weighted imaging (DWI), and we evaluated using PROPELLER-DWI for cancellation of MSAs of the pons in the patients who had MSAs on the EPI-DWI. MATERIALS AND METHODS: Sixty subjects (mean age: 58 years old and there were 30 men) who were classified according to the two types of sphenoid sinus underwent EPI-DWI. The two types of sphenoid sinus were classified by the degree of pneumatization on the sagittal T2-weighted image. The type-1 sphenoid sinus was 0% to less than 50% aeration of the bony sellar floor, and type-2 was 50% or more aeration of the boney sellar floor. Each of 10 subjects (n=20/60, mean age: 53) of the two types had PROPELLER and EPI-DWI performed simultaneously. We first evaluated the absence or presence of MSAs at the pons in the two types, and we compared EPI and PROPELLER-DWI in the subjects who underwent the two MR sequences simultaneously. We used 3.0T MR (Signa VHi, GE, MW, U.S.A.) with a standard head coil. All the MR images were interpreted by one neuroradiologiest. RESULTS: For the type-1, two (6.7%) cases had MSAs and 28 (93.7%) cases did not have MSAs on the EPI-DWI. For the type-2, twenty-seven (90%) cases had MSAs and 3 (10%) cases did not have MSAs on the EPI-DWI. The degree of pneumatization of the sphenoid sinus was related with the occurrence of MSAs of the pons, according to the chi-square test (p=0.000). All twenty cases who had PROPELLER-DWI performed had no MASs at the pons regardless of the type of sphenoid sinus. But all ten cases of type-2 produced MASs on the EPI-DWIs CONCLUSION: For EPI-DWI, a well aerated sphenoid sinus can induce MASs at the pons, and we should recognize this phenomenon to differentiate it from true infarcted lesion. PROPELLER DWI can be an optional tool to use for canceling this artifact.

Diffusion-Weighted Imaging of Brain Injury Due to Neonatal Hypoglycemia: A Case Report

Profound hypoglycemia results in significant brain injury because glucose is essential for normal brain functioning. We present here a case of transient neonatal hypoglycemia with diffuse brain injury. Magnetic resonance imaging was performed 2 days after onset, and this revealed bilateral regions of restricted diffusion in the parietal, occipital, frontal and temporal lobes. On the T1-weighted images, the regions showed indistinct gray matter-white matter differentiation. There were subtle high signal intensity lesions along the corresponding regions of the FLAIR and T2-weighted images.

Bright Intracranial Lesions on Diffusion-weighted Images: A Pictorial Review

Diffusion-weighted imaging (DWI) is a MR sequence that is used to evaluate the rate of microscopic water diffusion within the tissues. The ability to measure the rate of water diffusion is important because this is frequently altered in various disease processes. Generally, the lesions with restricted water diffusion show bright intensity on DWI, but the lesions without restricted water diffusion can also show bright intensity on DWI, which is called the "T2 shine through effect". With DWI, we can sensitively detect hyperacute infarction (within 6 hours after symptom onset), and this is difficult to detect with using CT and the conventional MR sequences. The acute and subacute lesions of hypoxic-ischemic encephalopathy and carbon monoxide intoxication also show bright intensity on the DWI. The other diseases that can show bright intensity on the DWI include acute and subacute diffuse axonal injury lesions, hyperacute and late subacute hematomas, cerebral abscess, subdural empyema, acute herpes encephalitis, various tumors and such degenerative and demyelinating diseases as multiple sclerosis, posterior reversible encephalopathy syndrome, Wilson's disease and Wernicke's encephalopathy.

Diffusion-Weighted MR Imaging in Acute Wernicke's Encephalopathy Associated with Pseudomembranous Colitis: A Case Report and Review of the Literature

Wernicke's encephalopathy is a common complication of thiamine deficiency among chronic alcoholics. However, there have been few reports about MR imaging findings, including the diffusion-weighted changes of this neurologic disorder, in nonalcoholic patients. We present here a rare case of acute Wernicke's encephalopathy that developed in a patient who received prolonged total parenteral nutrition for his pseudomembranous colitis. The MR imaging, including the diffusion-weighted imaging, was performed at the onset of disease and during follow-up. The diagnosis was made by the characteristic MR imaging findings and it was supported by the clinical features. The initial and follow-up MR imaging findings with diffusion-weighted imaging changes are described and correlated with the clinical status.

Assessment of Tissue Viability Using Diffusion- and Perfusion-Weighted MRI in Hyperacute Stroke

OBJECTIVE: The aim of this study was to investigate the relationship between the diffusion and perfusion parameters in hyperacute infarction, and we wanted to determine the viability threshold for the ischemic penumbra using diffusion- and perfusion-weighted imaging (DWI and PWI, respectively). MATERIALS AND METHODS: Both DWI and PWI were performed within six hours from the onset of symptoms for 12 patients who had suffered from acute stroke. Three regions of interest (ROIs) were identified: ROI 1 was the initial lesion on DWI; ROI 2 was the DWI/PWI mismatch area (the penumbra) that progressed onward to the infarct; and ROI 3 was the mismatch area that recovered to normal on the follow-up scans. The ratios of apparent diffusion coefficient (ADC), the relative cerebral blood volume (rCBV), and the time to peak (TTP) were calculated as the lesions' ROIs divided by the contralateral mirror ROIs, and these values were then correlated with each other. The viability threshold was determined by using the receiver operating characteristic (ROC) curves. RESULTS: For all three ROIs, the ADC ratios had significant linear correlation with the TTP ratios (p < 0.001), but not with the rCBV ratios (p = 0.280). There was no significant difference for the ADC and rCBV ratios within the ROIs. The mean TTP ratio/TTP delay between the penumbras' two ROIs showed a significant statistical difference (p < 0.001). The cutoff value between ROI 2 and ROI 3, as the viability threshold, was a TTP ratio of 1.29 (with a sensitivity and specificity of 86% and 73%, respectively) and a TTP delay of 7.8 sec (with a sensitivity and specificity of 84% and 72%, respectively). CONCLUSION: Determining the viability thresholds for the TTP ratio/delay on the PWI may be helpful for selecting those patients who would benefit from the various therapeutic interventions that can be used during the acute phase of ischemic stroke.

The Usefulness of Perfusion CT in Acute Cerebral Ischemic Infarction

PURPOSE: To determine the usefulness of cerebral perfusion computed tomography (CT) in patients with acute cerebral ischemic infarction. MATERIALS AND METHODS: Twelve patients with acute middle cerebral artery infarction underwent conventional CT and cerebral perfusion CT within 25 hours of the onset of symptoms. For each patient, perfusion CT scans were obtained at the levels of the basal ganglia and 1 cm caudal to them. Using special imaging software, perfusion imaging maps for cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP) were created, and the infarcted lesion was evaluated on each map. MTT and TTP delay times were measured in the perfusion defect lesion and symmetric contralateral normal cerebral hemisphere. Lesion size on each perfusion map was determined and compared with the value obtained by diffusionweighted MR imaging (DWMRI). RESULTS: In all patients, perfusion CT maps depicted the perfusion defect lesion, for which the MTT and TTP delay was remarkable. A comparison of lesion size between each perfusion map and DWMR images showed that the closest correlation involved CBF maps (8/12, 67%). On MTT maps, the lesion was larger than at DWMRI, suggesting that MTT mapping can be used to evaluate ischemic penumbra. CONCLUSION: Perfusion mapping facilitates the evaluation not only of the ischemic core and ischemic penumbra, but also of hemodynamic status in the area of the perfusion defect. This finding demonstrates that perfusion CT can be useful for the diagnosis and treatment of patients with acute cerebral ischemic infarction.

The Usefulness of Diffusion-weighted MR Imaging for Differentiation between Degenerative Spines and Infectious Spondylitis

PURPOSE: The differential diagnosis between Modic type I degenerative spine and infectious spondylitis sometimes is difficult, because the affected bone marrows in both disease show similar signal intensity on conventional MR imaging. We evaluate the usefulness of diffusion-wighted MR imaging for differential diagnosis between Modic type I degenerative spine and infectious spondylitis. MATERIALS AND METHODS: The spin-echo and diffusion-weighted MR images of eight patients with Modic type I degenerative spines and 14 patients with infectious spondylitis diagnosed by clinical findings or CTguided biopsies were analyzed. The diffusion-weighted imaging sequence was based on reversed fast imaging with steady-state precession (PSIF). Signal intensity changes of the vertebral bone marrow on conventional spin-echo and diffusion-weighted MR imaging were compared between degenerative spine and infectious spondylitis. RESULTS: On T1-weighted images, the affeted bone marrow in both disease showed hypointense signals. On T2-weighted images, all of type I degenerative spine and 11 of infectious spondylitis showed hyperintensity, and three of infectious spondylitis showed heterogeneous mixed signal intensity. On diffusionweighted MR images, all of type I degenerative spine were hypointense with peripheral high signal intensity to normal vertebral body, but infectious spondylitis was hyperintense (n=11) and hypointense (n=3). CONCLUSION: Diffusion-weighted MR imaging is useful to differentiate Modic type I degenerative spine from infectious spondylitis. On diffusion-weighted images, the high singal intensity of bone marrow suggests infectious spondylitis, whereas the low signal intensity of bone marrow with peripheral focal high signal intensity suggests type I degenerative spine.

Reversal of Apparent Diffusion Coefficient (ADC) Following Transient Focal Cerebral Ischemia in Cats

PURPOSE: To determine the minimal threshold ADC ratio suggesting reversible ischemia in a temporary model of MCAO. MATERIALS AND METHODS: Seven Korean cats weighing 3-3.5 kg were used as a temporary model of MCAO. The MCA was occluded for 1 hour, and diffusion-weighted images (DWI), and ADC and regional cerebral blood volume (rCBV) maps, were obtained at 1, 3, 6 and 24 hours after reperfusion using a 1.5T MR unit. The Cats were sacrificed 24 hours after imaging. Triphenyl tetrazolium chloride (TTC) staining of brain slices was performed, and DWI images and TTC-stained brain slices were compared with the naked eye. Reversible ischemia was defined as the area of high signal intensity at 1-hour DWI that normalized at follow-up DWI and in which TTC staining was normal. Using the ADC image obtained at 1 hour after reperfusion, 60 ADC ratios were obtained in the periphery of the infarct and reversible ischemia. Tissue survival showing normal TTC staining was used for final determination. The sensitivity and specificity of each ADC ratio was obtained and an ROC curve was plotted. RESULTS: Five of seven cats showed the reversible ischemia. An area of high signal intensity was seen on DWI images obtained 1 hour after reperfusion, and this improved at follow-up imaging. The distribution of the ADC ratio in the periphery of the infarct core was 0.71-0.81, and in the periphery of reversible ischemia it was 0.79-0.93. The ADC ratio of 0.80 obtained 1 hr after reperfusion predicted the survival of the ischemic tissue with 93% sensitivity and 90% specificity. The ADC ratio of the reversible ischemia was 0.82+/-0.03 at 1 hour after reperfusion, and this was higher than that of the infarct, which was 0.74+/-0.03. CONCLUSION: The minimal threshold ADC ratio suggesting reversible ischemia in this temporary model of MCAO was 0.80.

Clinical Usefulness of Diffusion-weighted MRI in Various Stages of Ischemic Stroke

PURPOSE: Diffusion-weighted MRI (DWI) is well known to be sensitive in the detection of hyperacute infarct, but has not been systematically investigated in patients with acute or subacute infarct. We evaluated the usefulness of diffusion-weighted MRI in assessing the various stages of brain infarct. MATERIALS AND METHODS: Fifty-five consecutive patients with symptoms of brain infarct underwent fast spinecho T2-weighted MRI (T2W1) and DWI. Using only a brief clinical history, two radiologists first attemptelto detect the lesion using T2W1, which was then compared with DWI. The usefulness of the latter was then evaluated in terms of the following criteria: 1) Its abilility to detect a lesion not seen at T2WI (detection); 2) localization of the responsible ischemic focus among multiple high-signal intensities seen at T2WI (localization); 3) conspicuity of a lesion which was subtle at T2WI (conspicuity); 4) detection of multiple lesions (multiplicity). RESULTS: DWI was useful in 44 of 55 patients (80%), including 9 of 9 (100%) with hyperacute infarct (<6 hours), 20 of 27 (74%) with acute infarct (<48 hours), and 15 of 19 (79%) with subacute infarct (<2 weeks). Among the nine patients at the hyperacute stage, DWI was useful for detection of the lesion in six (67%), for localization, 4 (44%) in one (11%), for conspicuity in four (44%), and for multiplicity in five (56%); at the acute stage (20 patients), for detection in three (15%), for localization in ten (50%), for conspicuity in eight (40%), and for moltiplicity in five (25%); and at the subacute stage (15 patients), for detection in three (20%), for localization in nine (60%), for conspicuity in two (13%), and for multiplicity in three (20%). CONCLUSION: DWI is very sensitive for the diagnosis of hyperacute infarct. In the assessment of this, it is useful during the acute or subacute period for the detection of small lesions, the localization of ongoing lesions among multiple high signal intensities seen at T2WI, and the determination of lesion conspicuity.

Diffusion-weighted MR Imaging of Intracerebral Hemorrhage

OBJECTIVE: To document the signal characteristics of intracerebral hemorrhage (ICH) at evolving stages on diffusion-weighted images (DWI) by comparison with conventional MR images. MATERIALS AND METHODS: In our retrospective study, 38 patients with ICH underwent a set of imaging sequences that included DWI, T1-and T2-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). In 33 and 10 patients, respectively, conventional and echo-planar T2* gradient-echo images were also obtained. According to the time interval between symptom onset and initial MRI, five stages were categorized: hyperacute (n=6); acute (n=7); early subacute (n=7); late subacute (n=10); and chronic (n=8). We investigated the signal intensity and apparent diffusion coefficient (ADC) of ICH and compared the signal intensities of hematomas at DWI and on conventional MR images. RESULTS: DWI showed that hematomas were hyperintense at the hyperacute and late subacute stages, and hypointense at the acute, early subacute and chronic stages. Invariably, focal hypointensity was observed within a hyperacute hematoma. At the hyperacute, acute and early subacute stages, hyperintense rims that corresponded with edema surrounding the hematoma were present. The mean ADC ratio was 0.73 at the hyperacute stage, 0.72 at the acute stage, 0.70 at the early subacute stage, 0.72 at the late subacute stage, and 2.56 at the chronic stage. CONCLUSION: DWI showed that the signal intensity of an ICH may be related to both its ADC value and the magnetic susceptibility effect. In patients with acute stroke, an understanding of the characteristic features of ICH seen at DWI can be helpful in both the characterization of intracranial hemorrhagic lesions and the differentiation of hemorrhage from ischemia.

Diffusion-Weighted MR Imaging in Biopsy-Proven Creutzfeldt-Jakob Disease

OBJECTIVE: To compare conventional and diffusion-weighted MR imaging in terms of their depiction of the abnormalities occurring in Creutzfeldt-Jakob disease. MATERIALS AND METHODS: We retrospectively analyzed the findings of conventional (T2-weighted and fluid-attenuated inversion recovery) and diffusion-weighted MR imaging in four patients with biopsy-proven Creutzfeldt-Jakob disease. The signal intensity of the lesion was classified by visual assessment as markedly high, slightly high, or isointense, relative to normal brain parenchyma. RESULTS: Both conventional and diffusion-weighted MR images demonstrated bilateral high signal intensity in the basal ganglia in all four patients. Cortical lesions were observed on diffusion-weighted MR images in all four, and on fluid-attenuated inversion recovery MR images in one, but in no patient on T2-weighted images. Conventional MR images showed slightly high signal intensity in all lesions, while diffusion-weighted images showed markedly high signal intensity in most. CONCLUSION: Diffusion-weighted MR imaging is more sensitive than its conventional counterpart in the depiction of Creutzfeldt-Jakob disease, and permits better detection of the lesion in both the cerebral cortices and basal ganglia.

Diffusion-Weighted MR Imaging in Animal Model with Acute Ischemic Brain Infarction: Evaluation of Reversible Brain Injury

PURPOSE: To determine whether the analysis of abnormally high signal intensities in ischemic tissue, as revealed by diffusion-weighted MR imaging (DWI) can be used to evaluate reversible brain lesions in a cat model of acute ischemia. MATERIALS AND METHODS: Ten cats were divided into two groups of five (Group I and Group II), and in all animals the middle cerebral artery was temporarily occluded. Group I underwent T2-DWI 30 minutes after occlusion, and Group II 120 minutes after occlusion. In both groups, DWI was performed one hour and 24 hours after reperfusion (at one hour, non-T2-weighted; at 24 hours, T2-weighted). Both occlusion and reperfusion were monitored by 99m TC-ECD brain perfusion SPECT. All animals were sacrificed 24 hours later and their brain tissue was stained with TTC. Signal intensity ratios (SIR, signifying average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region) of the two groups, as seen on DWI were compared. The percentage of hemispheric lesions occurring in the two groups was also compared. RESULTS: SIR after occlusion of the middle cerebral artery was 1.29 in Group I and 1.59 in Group II. Twenty-four hours after reperfusion, SIR in Group I was higher than in Group II (p<0.01). After occlusion and reperfusion, the percentage of hemispheric lesions in Group I was less than in Group II. For the latter, the percentage of these lesions revealed by TTC staining and T2-weighted imaging was 48% and 59%, respectively, findings distinctly different from those for Group I. In addition, in group I, infarction was revealed by neither TTC staining nor T2-weighted imaging (p<0.01). CONCLUSION: The use of DWI to evaluate signal intensity ratios can help determine whether or not brain injury after temporary cerebral ischemia is reversible.