Non-Contrast-Enhanced Silent Scan MR Angiography of Intracranial Anterior Circulation Aneurysms Treated with a Low-Profile Visualized Intraluminal Support Device.

BACKGROUND AND PURPOSE: The Low-Profile Visualized Intraluminal Support Device comprises a small-cell nitinol structure and a single-wire braided stent that provides greater metal coverage than previously reported intracranial stents, as well as assumed strong susceptibility artifacts. This study aimed to assess the benefits of non-contrast-enhanced MRA by using a Silent Scan (Silent MRA) for intracranial anterior circulation aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents. MATERIALS AND METHODS: Thirty-one aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents were assessed by using Silent MRA, 3D TOF-MRA, and x-ray DSA. The quality of MRA visualization of the reconstructed artery was graded on a 4-point scale from 1 (not visible) to 4 (excellent). Aneurysm occlusion status was evaluated by using a 2-grade scale (total occlusion/remnant [neck or aneurysm]). Weighted κ statistics were used to evaluate interobserver and intermodality agreement. RESULTS: The mean scores ± SDs for Silent MRA and 3D TOF-MRA were 3.16 ± 0.79 and 1.48 ± 0.67 (P < .05), respectively, with substantial interobserver agreement (κ = 0.66). The aneurysm occlusion rates of the 2-grade scale (total occlusion/remnant [neck or aneurysm]) were 69%/31% for DSA, 65%/35% for Silent MRA, and 92%/8% for 3D TOF-MRA, respectively. The intermodality agreements were 0.88 and 0.30 for DSA/Silent MRA and DSA/3D TOF-MRA, respectively. CONCLUSIONS: Silent MRA seems to be useful for visualizing intracranial anterior circulation aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents.

Synthetic MRI in the Detection of Multiple Sclerosis Plaques.

BACKGROUND AND PURPOSE: Synthetic MR imaging enables the creation of various contrast-weighted images including double inversion recovery and phase-sensitive inversion recovery from a single MR imaging quantification scan. Here, we assessed whether synthetic MR imaging is suitable for detecting MS plaques. MATERIALS AND METHODS: Quantitative and conventional MR imaging data on 12 patients with MS were retrospectively analyzed. Synthetic T2-weighted, FLAIR, double inversion recovery, and phase-sensitive inversion recovery images were produced after quantification of T1 and T2 values and proton density. Double inversion recovery images were optimized for each patient by adjusting the TI. The number of visible plaques was determined by a radiologist for a set of these 4 types of synthetic MR images and a set of conventional T1-weighted inversion recovery, T2-weighted, and FLAIR images. Conventional 3D double inversion recovery and other available images were used as the criterion standard. The total acquisition time of synthetic MR imaging was 7 minutes 12 seconds and that of conventional MR imaging was 6 minutes 29 seconds The lesion-to-WM contrast and lesion-to-WM contrast-to-noise ratio were calculated and compared between synthetic and conventional double inversion recovery images. RESULTS: The total plaques detected by synthetic and conventional MR images were 157 and 139, respectively (P = .014). The lesion-to-WM contrast and contrast-to-noise ratio on synthetic double inversion recovery images were superior to those on conventional double inversion recovery images (P = .001 and < 0.001, respectively). CONCLUSIONS: Synthetic MR imaging enabled detection of more MS plaques than conventional MR imaging in a comparable acquisition time. The contrast for MS plaques on synthetic double inversion recovery images was better than on conventional double inversion recovery images.

Usefulness of Non-Contrast-Enhanced MR Angiography Using a Silent Scan for Follow-Up after Y-Configuration Stent-Assisted Coil Embolization for Basilar Tip Aneurysms.

BACKGROUND AND PURPOSE: Y-configuration stent-assisted coil embolization is used for treating wide-neck aneurysms. Noninvasive alternatives to x-ray DSA for follow-up after Y-configuration stent-assisted coil embolization treatment are required. This study aimed to assess the usefulness of non-contrast-enhanced MRA by using a Silent Scan (silent MRA) for follow-up after Y-configuration stent-assisted coil embolization for basilar tip aneurysms. MATERIALS AND METHODS: Seven patients treated with Y-configuration stent-assisted coil embolization for basilar tip aneurysms underwent silent MRA, 3D TOF-MRA, and DSA. Silent MRA and 3D TOF-MRA images were obtained during the same scan session on a 3T MR imaging system. Two neuroradiologists independently reviewed both types of MRA images and subjectively scored the flow in the stents on a scale of 1 (not visible) to 5 (nearly equal to DSA) by referring to the latest DSA image as a criterion standard. Furthermore, we evaluated the visualization of the neck remnant. RESULTS: In all patients, the 2 observers gave a higher score for the flow in the stents on silent MRA than on 3D TOF-MRA. The average score ± standard deviation was 4.07 ± 0.70 for silent MRA and 1.93 ± 0.80 (P < .05) for 3D TOF-MRA. Neck remnants were depicted by DSA in 5 patients. In silent MRA, neck remnants were depicted in 5 patients, and visualization was similar to DSA; however, in 3D TOF-MRA, neck remnants were depicted in only 1 patient. CONCLUSIONS: Silent MRA might be useful for follow-up after Y-configuration stent-assisted coil embolization.

Utility of a Multiparametric Quantitative MRI Model That Assesses Myelin and Edema for Evaluating Plaques, Periplaque White Matter, and Normal-Appearing White Matter in Patients with Multiple Sclerosis: A Feasibility Study.

BACKGROUND AND PURPOSE: T1 and T2 values and proton density can now be quantified on the basis of a single MR acquisition. The myelin and edema in a voxel can also be estimated from these values. The purpose of this study was to evaluate a multiparametric quantitative MR imaging model that assesses myelin and edema for characterizing plaques, periplaque white matter, and normal-appearing white matter in patients with MS. MATERIALS AND METHODS: We examined 3T quantitative MR imaging data from 21 patients with MS. The myelin partial volume, excess parenchymal water partial volume, the inverse of T1 and transverse T2 relaxation times (R1, R2), and proton density were compared among plaques, periplaque white matter, and normal-appearing white matter. RESULTS: All metrics differed significantly across the 3 groups (P < .001). Those in plaques differed most from those in normal-appearing white matter. The percentage changes of the metrics in plaques and periplaque white matter relative to normal-appearing white matter were significantly more different from zero for myelin partial volume (mean, -61.59 ± 20.28% [plaque relative to normal-appearing white matter], and mean, -10.51 ± 11.41% [periplaque white matter relative to normal-appearing white matter]), and excess parenchymal water partial volume (13.82 × 103 ± 49.47 × 103% and 51.33 × 102 ± 155.31 × 102%) than for R1 (-35.23 ± 13.93% and -6.08 ± 8.66%), R2 (-21.06 ± 11.39% and -4.79 ± 6.79%), and proton density (23.37 ± 10.30% and 3.37 ± 4.24%). CONCLUSIONS: Multiparametric quantitative MR imaging captures white matter damage in MS. Myelin partial volume and excess parenchymal water partial volume are more sensitive to the MS disease process than R1, R2, and proton density.

Assessing Blood Flow in an Intracranial Stent: A Feasibility Study of MR Angiography Using a Silent Scan after Stent-Assisted Coil Embolization for Anterior Circulation Aneurysms.

BACKGROUND AND PURPOSE: Blood flow in an intracranial stent cannot be visualized with 3D time-of-flight MR angiography owing to magnetic susceptibility and radiofrequency shielding. As a novel follow-up tool after stent-assisted coil embolization, we applied MRA by using a Silent Scan algorithm that contains an ultrashort TE combined with an arterial spin-labeling technique (Silent MRA). The purpose of this study was to determine whether Silent MRA could visualize flow in an intracranial stent placed in the anterior circulation. MATERIALS AND METHODS: Nine patients treated with stent-assisted coil embolization for anterior circulation aneurysms underwent MRAs (Silent MRA and TOF MRA) and x-ray digital subtraction angiography. MRAs were performed in the same session on a 3T unit. Two neuroradiologists independently reviewed the MRA images and subjectively scored flow in a stent as 1 (not visible) to 4 (excellent) by referring to the latest x-ray digital subtraction angiography image as a criterion standard. RESULTS: Both observers gave MRA higher scores than TOF MRA for flow in a stent in all cases. The mean score for Silent MRA was 3.44 ± 0.53, and for TOF MRA, it was 1.44 ± 0.46 (P < .001). CONCLUSIONS: Silent MRA was able to visualize flow in an intracranial stent more effectively than TOF MRA. Silent MRA might be useful for follow-up imaging after stent-assisted coil embolization, though these study results may be only preliminary due to some limitations.

Dynamic alteration of regional cerebral blood flow during carotid compression and proof of reversibility.

BACKGROUND: It is difficult to non-invasively visualize changes in regional cerebral blood flow caused by manual compression of the carotid artery. PURPOSE: To visualize dynamic changes in regional cerebral blood flow during and after manual compression of the carotid artery. MATERIAL AND METHODS: Two healthy volunteers were recruited. Anatomic features and flow directions in the circle of Willis were evaluated with time-of-flight magnetic resonance angiography (MRA) and two-dimensional phase-contrast (2DPC) MRA, respectively. Regional cerebral blood flow was visualized with territorial arterial spin-labeling magnetic resonance imaging (TASL-MRI). TASL-MRI and 2DPC-MRA were performed in three states: at rest, during manual compression of the right carotid artery, and after decompression. In one volunteer, time-space labeling inversion pulse (Time-SLIP) MRA was performed to confirm collateral flow. RESULTS: During manual carotid compression, in one volunteer, the right thalamus changed to be fed only by the vertebrobasilar system, and the right basal ganglia changed to be fed by the left internal carotid artery. In the other volunteer, the right basal ganglia changed to be fed by the vertebrobasilar system. 2DPC-MRA showed that the flow direction changed in the right A1 segment of the anterior cerebral artery and the right posterior communicating artery. Perfusion patterns and flow directions recovered after decompression. Time-SLIP MRA showed pial vessels and dural collateral circulation when the right carotid artery was manually compressed. CONCLUSION: Use of TASL-MRI and 2DPC-MRA was successful for non-invasive visualization of the dynamic changes in regional cerebral blood flow during and after manual carotid compression.

Urine diacetylspermine as a novel tumour maker for pancreatobiliary carcinomas.

BACKGROUND: Serum carcinoembryonic antigen (highly specific) and carbohydrate antigen 19-9 (highly sensitive) have been used as tumour markers for pancreatobiliary cancers. A novel urine tumour marker, diacetylspermine, was compared with the two conventional serum tumour markers in 125 patients with pancreatobiliary diseases. RESULTS: When the diagnosis of benign or malignant condition was examined, the sensitivity of urine diacetylspermine (75%) was higher than that of serum carcinoembryonic antigen (44%; P=0.048) and the same as that of serum carbohydrate antigen 19-9 (75%). The specificity of urine diacetylspermine (81%) was lower than that of serum CEA (92%) and as high as that of serum carbohydrate antigen 19-9 (80%). The efficiency of urine diacetylspermine (79%) was higher than that of serum carcinoembryonic antigen (74%) and the same as that of serum carbohydrate antigen 19-9 (79%). CONCLUSION: These results suggest that urine diacetylspermine is a marker for pancreatobiliary carcinoma, which is as highly sensitive and specific as serum carbohydrate antigen 19-9.

Evidence for a novel racemization process of an asparaginyl residue in mouse lysozyme under physiological conditions.

We examined chemical reactions in mouse lysozyme after incubation under physiological conditions (pH 7 and 37 degrees C). After incubation for 8 weeks, racemization was observed specifically at Asn127 among the 19 Asp/Asn residues in mouse lysozyme. Furthermore, analysis of the primary structure showed that the racemized residue was not Asp, but Asn, which demonstrates that deamidation and isomerization did not occur. These results mean that this racemization occurs without forming a succinimide intermediate. This is the first example of D-asparaginyl formation in a protein occurring during the racemization process under physiological conditions.

8-oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts.

BACKGROUND: Reactive oxygen species (ROS) can cause an oxidative modification of nucleotides, such as 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), which can lead to defects in DNA replication. The misincorporation of 8-oxo-dGTP into DNA is prevented by 8-oxo-dGTPase, which hydrolyzes 8-oxo-dGTP into 8-oxo-dGMP. The changes in this defensive system have not yet been examined in failing hearts, in which the generation of ROS increases. METHODS AND RESULTS: Myocardial infarction (MI) was created in mice by ligating the left coronary artery. Four weeks later, the left ventricle was dilated and contractility was diminished on echocardiography. The generation of ROS, as measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, increased in the noninfarcted left ventricle from MI mice. The formation of thiobarbituric acid-reactive substances also increased in the mitochondria from MI mice. 8-Oxo-dGTPase was detected in the mitochondrial fractions isolated from MI mice using a Western blot analysis with an antibody to its human homologue (hMTH1). Immunohistochemistry showed positive staining for hMTH1 was localized in the cardiac myocytes. CONCLUSIONS: The level of 8-oxo-dGTPase increased in the mitochondria isolated from post-MI hearts as oxidative stress increased, thus suggesting that a preventive mechanism is activated against ROS-induced DNA damage. As a result, 8-oxo-dGTPase is considered a useful marker of mitochondrial oxidative stress in heart failure.

a4, a unique kidney-specific isoform of mouse vacuolar H+-ATPase subunit a.

The vacuolar-type H+ -ATPase (V-ATPase) translocates protons across membranes. Here, we have identified a mouse cDNA coding for a fourth isoform (a4) of the membrane sector subunit a of V-ATPase. This isoform was specifically expressed in kidney, but not in the heart, brain, spleen, lung, liver, muscle, or testis. Immunoprecipitation experiments, together with sequence similarities for other isoforms (a1, a2, and a3), indicate that the a4 isoform is a component of V-ATPase. Moreover, histochemical studies show that a4 is localized in the apical and basolateral plasma membranes of cortical alpha- and beta-intercalated cells, respectively. These results suggest that the V-ATPase, with the a4 isoform, is important for renal acid/base homeostasis.

Expression of lysosome-associated membrane proteins in human colorectal neoplasms and inflammatory diseases.

The lysosome-associated membrane proteins (LAMPs)-1 and -2 are major constituents of the lysosomal membrane. These molecules are known to be among the most glycosylated proteins of several types of cells and cancer cells, and their expression in cancer cells is marked by a distinct difference in the structures of the oligosaccharides as compared to nonmalignant cells. We analyzed by immunohistochemistry the intensity and distribution of LAMP-1 and LAMP-2 in 9 human colorectal cancer cases and in 16 control cases, including inflammatory diseases (diverticulitis, ulcerative colitis, and Crohn's disease). LAMP proteins were expressed more intensely in the epithelium of colorectal neoplasms than in normal mucosa (P < 0.05), and no significant differences were found between adenoma and cancer cells (P > 0.05) in the same tissue section. Further, in sites of inactive inflammatory diseases and nonneoplastic areas in cancer specimens, no significant increases in epithelial LAMP proteins were observed, even in the proliferative zone of the lower crypt epithelium. Northern blot analysis showed increased expression of LAMP-1 and LAMP-2A in two of three colorectal cancers examined and increased LAMP-2B in all three cancers. Our findings suggest that LAMPs are related to neoplastic progression, but there is no direct association between the expression of LAMP molecules and cell proliferation.

Both heavy strand replication origins are active in partially duplicated human mitochondrial DNAs.

The replication of human mitochondrial DNA (mtDNA) is initiated from a pair of displaced origins, one priming continuous synthesis of daughter-strand DNA from the heavy strand (OH) and the other priming continuous synthesis from the light strand (OL). In patients with sporadic large-scale rearrangements of mitochondrial DNA (i.e., partially-deleted [Delta-mtDNA] and partially-duplicated [dup-mtDNA] molecules), the dup-mtDNAs typically contain extra origins of replication, but it is unknown at present whether they are competent for initiation of replication. Using cybrids harboring each of two types of dup-mtDNAs-one containing two OHs and two OLs, and one containing two OHs and one OL-we used ligation-mediated polymerase chain reaction (LMPCR) to measure the presence and relative amounts of nascent heavy strands originating from each OH. We found that the nascent heavy strands originated almost equally from the two OHs in each cell line, indicating that the extra OH present on a partially duplicated mtDNA is competent for heavy strand synthesis. This extra OH could potentially confer a replicative advantage to dup-mtDNAs, as these molecules may have twice as many opportunities to initiate replication compared to wild-type (or partially deleted) molecules.

[Effects of preserved erythrocytes and activated-preserved erythrocytes with phosphoenolpyruvate on energy metabolism in rat ischemic brain tissue].

The effects of erythrocyte function on cerebral ischemia were studied from the perspective of filtration capability (deformability) and total oxygen delivery. Erythrocytes of Wistar rats were divided into three groups: fresh blood, preserved blood, and activated preserved blood (preserved erythrocytes in which total oxygen delivery was increased with phosphoenolpyruvate). Filtration capability was calculated and evaluated by a filtration technique, while total oxygen delivery was evaluated by calculating the efficiency of oxygen delivery from an oxygen dissociation curve. Exchange transfusion was performed in spontaneously hypertensive rats with each of these groups at the same hemoglobin concentration. Bilateral carotid arteries were then ligated for one hour, and, cerebral blood flow and concentrations of adenine nucleotide and lactic acid in cerebral tissue were measured. The filtration capability of both preserved blood and activated preserved blood decreased to about one-third that of fresh blood. The efficiency of oxygen delivery after blood transfusion decreased to 17% with preserved blood, which was about half that (35%) with fresh blood. In the group of with activated preserved blood, this rate increased to 52%. The adenylate energy charge (E.C.) in brain tissue markedly decreased to 0.27 with preserved blood, which was much lower than the value (0.74) with fresh blood. With activated preserved blood, the E.C. value was 0.39. Thus, the decrease in E.C. was mild. With regard to the lactic acid concentration in brain tissue, the value with fresh blood was 12 mumoles/g tissue, while that with preserved blood was 24 mumoles/g tissue, and that with activated preserved blood was 18 mumoles/g tissue. With respect to cerebral blood flow, the values with preserved blood and activated preserved blood decreased to about one-half that with fresh blood. These results suggest that an increase in total oxygen delivery by erythrocytes contributes to improving energy metabolism in brain tissue during cerebral ischemia, and particularly during poor microcirculation.

[Clinical laboratory data and reference intervals standardized in Fukuoka].

In Fukuoka whose population is approximately five million inhabitants, surveys on the accuracy of laboratory data have been performed by the Fukuoka Prefecture Medical Association for the last 30 years. We have been attempting to evaluate the data for routine use since 1988, and it has become possible to share laboratory data between all institutions in Fukuoka prefectures. As a result, reference intervals for 23 clinical chemistry analytes were established in 1995, to which were added in 1996 five serum protein constituents that have been utilized for clinical examinations. Methods for documentations and monitorings the data obtained in the prefecture were also established, standardization of the above analytes extended to 97% of the institutions in the prefecture. Results for 14 of the 23 clinical chemistry analytes have become highly reliable and clinically useful as differences between institutions in terms of results have narrowed. Standardization of other analytes is now in progress.

Standardization of laboratory data and establishment of reference intervals in the Fukuoka Prefecture: a Japanese perspective.

Standardization of 22 clinical chemistry analytes and five serum protein constituents has been performed in the Fukuoka Prefecture, which has a population of approximately five million. The standardization project was established to determine reference intervals for these analytes by educating physicians, medical technologists and staff of medical institutions, and by daily or monthly monitoring the use of common control samples through e-mail. Standardization extended to 97% of the institutions in the prefecture. Results for 14 of the 22 clinical chemistry analytes have become highly reliable and differences between institutions decreased. Standardization of other analytes is now in progress. Regional collaboration based on international guidelines led to a significant improvement in interlaboratory comparability. Areas where further improvements are needed have been identified.

Activation of the lectin complement pathway by ficolins.

Mannose-binding lectin (MBL), a serum lectin specific for mannose or N-acetylglucosamine (GlcNAc), which contains both a collagen-like domain and a carbohydrate-recognition domain (CRD), plays a role in innate immunity by acting as an opsonin and activating complement in association with MBL-associated serine protease (MASP) via the lectin pathway. Another type of GlcNAc-binding lectins termed "ficolins" exist in serum. They are characterized by the presence of both a collagen-like domain and a fibrinogen-like domain. Investigations of two types of human serum ficolins, ficolin/P35 and Hakata antigen, revealed that they are associated with MASPs and sMAP, a truncated protein of MASP-2, and activate complement. These findings indicate that, like MBL, serum ficolins are collagenous lectins capable of activating the lectin pathway and thus have a role in innate immunity.

[Primary thalamic hemorrhage penetrating to the lateral ventricle in an infant with abnormal protein S(protein S-Tokushima)].

We experienced a 3 months infant with thalamic hemorrhage penetrating to lateral ventricle with abnormal Protein S. Although the coagulation factor and fibrinogenolysis factors were evaluated, there were no remarkable abnormal laboratory data except for slightly decline of Protein S. The DNA analysis was performed for Protein S, and a missense mutation(A to G transmission) was found, which was resulting in Lys-155 to Glu. The total Protein S antigen was normal level, but co-factor activity for activated Protein C was declined. That mutation is named Protein S-Tokushima, and the patient who has abnormal Protein S tends to suffer recurrent coagulopathy. In our patient, it was interesting that any thrombotic disease had not occurred, but cerebral hemorrhage had occurred.