FLAIR sequences reliably provide diagnostic images in patients with acute SAH.

Cerebral vascular mean transit time (MTT), defined as the ratio of cerebral blood volume to cerebral blood flow (CBV/CBF), is a valuable indicator of the cerebral circulation. Positron emission tomography (PET) and dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) are useful for the quantitative determination of MTT in the clinical setting. The aim of this study was to establish a normal value set of MTT as determined by PET and by DSC-MRI and to identify differences between these methods. Seven healthy volunteers were studied with 15 O-PET (H 2 15 O and C 15 O) and gradient-echo echo-planar DSC-MRI at 1.5 T. In the DSC-MRI study with bolus injection of contrast agent, deconvolution analysis was performed. Comparison of gray-to-white matter ratios showed fairly good agreement between PET and DSC-MRI for all parameters (relative CBV, relative CBF, and relative MTT), confirming the validity of relative measurements with DSC-MRI. However, quantitative MTT measured by DSC-MRI was significantly shorter than that measured by PET in cerebral cortical regions (2.8 to 3.0 secs for DSC-MRI versus 3.9 to 4.3 secs for PET) and the centrum semiovale (3.5 secs for DSC-MRI versus 4.8 secs for PET). These discrepancies may be because of the differences in the intrinsic sensitivity of each imaging modality to vascular components; whereas PET measurement of CBV is equally sensitive to all vascular components, measurement with DSC-MRI originates from the microvasculature in the vicinity of the brain parenchyma. This underlying difference may influence interpretation of MTT determined by PET or by DSC-MRI for patients with cerebrovascular disease.

We attempted to detect circulating hepatocellular carcinoma by demonstrating hepatocyte-associated mRNA in the nuclear cell component of peripheral blood using nested reverse transcription-polymerase chain reaction because of the extremely small number of tumor cells in the circulation. Albumin mRNA was demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse transcription-polymerase chain reaction. In contrast, alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating the possibility of using alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. alpha-Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17 cases of chronic hepatitis (12%). alpha-Fetoprotein mRNA was not demonstrated in 26 cases of normal healthy volunteers (0%). Among the patients with hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and serum alpha-fetoprotein level were markedly increased in the patients with alpha-fetoprotein mRNA in blood. In addition, alpha-fetoprotein mRNA was detected in the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.

Background and Purpose-Acute decreases in the MR T2*-weighted signal have been reported in experimental models of middle cerebral artery occlusion. This has been attributed to blood deoxygenation in association with an increased brain oxygen extraction fraction. The aim of this study was to detect this signal by susceptibility-weighted MR imaging in acute ischemic stroke patients. Methods-Dynamic susceptibility contrast-enhanced MR (DSC-MR) imaging was performed within 4 hours of stroke onset in 6 patients with unilateral cerebral artery occlusion (middle cerebral artery, nϭ5; internal carotid artery, nϭ1). Cerebral blood volume was estimated on a pixel-by-pixel basis. DSC-MR images taken before arrival of the contrast medium were examined visually to identify hypointense areas. Bilateral regions of interest were set in the middle cerebral artery territory for comparison of the mean signal intensity. A semilogarithmic plot of signal intensity versus cerebral blood volume for every pixel in the region of interest was also analyzed. Results-The side on which the hypointense area was seen was significantly correlated with the side of arterial occlusion.The mean signal intensity was significantly smaller on the affected side than on the contralateral side. The semilogarithmic plot of signal intensity versus cerebral blood volume indicated greater deoxyhemoglobin concentrations for the ipsilateral than for the contralateral region of interest. Conclusions-DSC-MR

Hypoperfusion of the cerebral white matter and basal ganglia in asymptomatic WML subjects may be induced by the arteriosclerosis of long penetrating medullary arteries and lenticulostriate arteries but may not be directly related to the production of WML. The role of hypoperfusion in the production of WML and acceleration of its development remains to be elucidated.

Volume expansion associated with brain infarction occurs in perfusion-diffusion mismatch of magnetic resonance imaging. We aimed at elucidating the metabolic impairment of this phenomenon with (15)O positron emission tomography and perfusion and diffusion magnetic resonance imaging. Eleven patients with acute unilateral embolic occlusion of the internal carotid or middle cerebral artery were studied within 6 hours of onset. Regional cerebral blood flow and cerebral metabolic rate of oxygen (CMRO(2)) were compared with those in the contralateral cerebral hemisphere. The relative apparent diffusion coefficient of water was estimated as a marker of cytotoxic edema. Relative cerebral blood flow and relative CMRO(2) in an evolving infarct (normal diffusion initially, but abnormal on day 3) were significantly (p < 0.05) less than those in the periinfarct area (normal diffusion initially and on day 3). The relative apparent diffusion coefficient between the evolving infarct and periinfarct showed no significant difference. These findings indicated that the initial 3-day volume expansion of an embolic brain infarction was associated with disturbed CMRD(2) but not with cytotoxic edema as early as 6 hours after onset. The "metabolic penumbra" defined as normal water diffusion with depressed CMRO(2) is a target to reduce the volume expansion of brain infarction.

Cerebral blood flow (CBF) and vascular mean transit time (MTT) can be determined by dynamic susceptibility contrast-enhanced magnetic resonance imaging and deconvolution with an arterial input function. However, deconvolution by a singular value decomposition (SVD) method is sensitive to the tracer delay that often occurs in patients with cerebrovascular disease. We investigated the effect of tracer delay on CBF determined by SVD deconvolution. Simulation study showed that underestimation of CBF due to tracer delay was larger for shorter MTTs. We developed a delay correction method that determines tracer delay by means of least-squares fitting pixel-by-pixel. The corrected CBF was determined by SVD deconvolution after time-shifting of the measured concentration curve. The simulations showed that the corrected CBF was insensitive to tracer delay irrespective of the vascular model, although CBF fluctuation increased slightly. We applied the delay correction to the CBF and MTT images acquired for nine patients with hyperacute stroke and unilateral occlusion of the middle cerebral artery. We found in some patients that the delay correction modulated the contrast of CBF and MTT images. For hyperacute stroke patients, tracer delay correction is essential to obtain reliable perfusion image when SVD deconvolution is used.

The p53 gene is currently considered to function as a tumor-suppressor gene in various human malignancies. In hematologic malignancies, alterations in the p53 gene have been shown in some human leukemias and lymphomas. Although mutations in the p53 gene are infrequent in acute myelogenous leukemia (AML) patients, we show in this report that alterations in the p53 gene are frequent in myeloid leukemia cell lines. We studied alterations of the p53 gene in nine human myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP) analysis, and direct sequencing. Expression of the p53 gene was not detected at all by RT-PCR in two of the nine cell lines. In these two cell lines, Southern blot analysis showed gross rearrangements and deletions in both of the p53 alleles. Six of the nine cell lines were found to express only mutant p53 mRNA by RT-PCR/SSCP analysis and direct sequencing, and wild-type p53 mRNA was not detected. Two of the mutant p53 mRNAs were shown to be products of abnormal splicing events induced by intronic point mutations. Taken together, eight of nine human myeloid leukemia cell lines expressed no or an undetectable amount of wild-type p53 mRNA. Three of the eight cell lines were growth factor- dependent. Our results suggest that inactivation of the p53 gene may be a common feature in myeloid leukemia cell lines and may play an important role in the establishment of these cell lines.