Ako Sasao

Prognostic Value of Perfusion MR Imaging of High-Grade Astrocytomas: Long-Term Follow-Up Study

BACKGROUND AND PURPOSE: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma. MATERIALS AND METHODS: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23–76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors. RESULTS: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (≤2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163–29.788), maximum rCBV (4.739; 95% CI, 1.950–11.518), extent of surgery (2.692; 95% CI, 1.196–6.061), and sex (2.632; 95% CI, 1.153–6.010). CONCLUSION: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

Evaluation of Dural Arteriovenous Fistulas with 4D Contrast-Enhanced MR Angiography at 3T

BACKGROUND AND PURPOSE: Four-dimensional contrast-enhanced MR angiography (4D-CE-MRA) at 3T may replace digital subtraction angiography (DSA) for certain diagnostic purposes in patients with intracranial dural arteriovenous fistula (DAVF). The aim of this study was to test the hypothesis that 4D-CE-MRA at 3T enables the same characterization of intracranial DAVFs as DSA. MATERIALS AND METHODS: The study population consisted of 18 consecutive patients with intracranial DAVFs (11 women, 7 men; age range, 35–82 years; mean age, 64.8 years). They underwent 4D-CE-MRA at 3T and DSA. The 4D-CE-MRA series combined randomly segmented central k-space ordering, keyhole imaging, sensitivity encoding, and half-Fourier imaging. We obtained 30 dynamic scans every 1.9 seconds with a spatial resolution of 1 × 1 × 1.5 mm. Two independent readers reviewed the 4D-CE-MRA images for main arterial feeders, fistula site, and venous drainage. Interobserver and intermodality agreement was assessed by κ statistics. RESULTS: At DSA, 8 fistulas were located at the transverse sigmoid sinus; 8, at the cavernous sinus; and 2, at the sinus adjacent to the foramen magnum. Interobserver agreement was fair for the main arterial feeders (κ = 0.59), excellent for the fistula site (κ = 0.91), and good for venous drainage (κ = 0.86). Intermodality agreement was moderate for the main arterial feeders (κ = 0.68) and excellent for the fistula site (κ = 1.0) and venous drainage (κ = 1.0). CONCLUSIONS: The agreement between 4D-CE-MRA and DSA findings was good to excellent with respect to the fistula site and venous drainage.

Comparison of the Added Value of Contrast-Enhanced 3D Fluid-Attenuated Inversion Recovery and Magnetization-Prepared Rapid Acquisition of Gradient Echo Sequences in Relation to Conventional Postcontrast T1-Weighted Images for the Evaluation of Leptomeningeal Diseases at 3T

BACKGROUND AND PURPOSE: The usefulness of contrast-enhanced 3D T2-FLAIR MR imaging for the evaluation of leptomeningeal diseases has not been systematically investigated. The purpose of this study was to assess the value added by contrast-enhanced 3D T2-FLAIR and MPRAGE sequences to conventional postcontrast T1-weighted images in the evaluation of leptomeningeal diseases. We also undertook in vitro studies in attempts to understand the consequences of our patient study. MATERIALS AND METHODS: Twelve patients with confirmed leptomeningeal diseases underwent postcontrast T1-weighted, MPRAGE, and 3D T2-FLAIR imaging at 3T. Two radiologists independently assessed the presence of additional information on postcontrast 3D MR images compared with postcontrast T1-weighted images. The effect of different Gd concentrations and flow velocities on the signal intensity on 3D T2-FLAIR images was investigated in vitro. RESULTS: According to both reviewers, 3D T2-FLAIR images yielded significantly more information than did MPRAGE images (P < .05 and P < .01, respectively). In the in vitro study, 3D T2-FLAIR was more highly sensitive to low Gd concentrations and less sensitive to high Gd concentrations than were T1-weighted or MPRAGE sequences. On 3D T2-FLAIR sequences, at a flow velocity exceeding 1.0 cm/s, the signal intensity of blood-mimicking fluids at concentrations of 0 and 0.1 mmol/L was as low as at 1.3 mmol/L. CONCLUSIONS: For the depiction of leptomeningeal diseases, postcontrast 3D T2-FLAIR provides more additional information than postcontrast MPRAGE imaging. The superiority of the 3D T2-FLAIR sequence is associated with its high sensitivity to flow.

Quantitative Blood Flow Measurements in Gliomas Using Arterial Spin-Labeling at 3T: Intermodality Agreement and Inter- and Intraobserver Reproducibility Study

BACKGROUND AND PURPOSE: QUASAR is a particular application of the ASL method and facilitates the user-independent quantification of brain perfusion. The purpose of this study was to assess the intermodality agreement of TBF measurements obtained with ASL and DSC MR imaging and the inter- and intraobserver reproducibility of glioma TBF measurements acquired by ASL at 3T. MATERIALS AND METHODS: Two observers independently measured TBF in 24 patients with histologically proved glioma. ASL MR imaging with QUASAR and DSC MR imaging were performed on 3T scanners. The observers placed 5 regions of interest in the solid tumor on rCBF maps derived from ASL and DSC MR images and 1 region of interest in the contralateral brain and recorded the measured values. Maximum and average sTBF values were calculated. Intermodality and intra- and interobsever agreement were determined by using 95% Bland-Altman limits of agreement and ICCs. RESULTS: The intermodality agreement for maximum sTBF was good to excellent on DSC and ASL images; ICCs ranged from 0.718 to 0.884. The 95% limits of agreement ranged from 59.2% to 65.4% of the mean. ICCs for intra- and interobserver agreement for maximum sTBF ranged from 0.843 to 0.850 and from 0.626 to 0.665, respectively. The reproducibility of maximum sTBF measurements obtained by methods was similar. CONCLUSIONS: In the evaluation of sTBF in gliomas, ASL with QUASAR at 3T yielded measurements and reproducibility similar to those of DSC perfusion MR imaging.

Differentiation between paraclinoid and cavernous sinus aneurysms with contrast-enhanced 3D constructive interference in steady-state MR imaging

BACKGROUND AND PURPOSE: Differentiation between paraclinoid and cavernous sinus aneurysms of the internal carotid artery (ICA) is critical when considering treatment options. The purpose of this study was to determine whether contrast-enhanced (CE) 3D constructive interference in steady state (CISS) MR imaging is useful to differentiate between paraclinoid and cavernous sinus aneurysms. MATERIALS AND METHODS: This study included 11 aneurysms in 10 consecutive female patients, ranging from 52 to 66 years of age. All aneurysms were adjacent to the anterior clinoid process. After conventional and CE 3D-CISS imaging on a 1.5T MR imaging unit, all patients underwent surgery, and the relationship between the aneurysms and the dura was confirmed. Two neuroradiologists evaluated the location of the aneurysms on CE 3D-CISS images and classified them as intradural, partially intradural, and extradural aneurysms. Operative findings were used as a reference standard. To understand the imaging characteristics, we assessed the boundary and signal intensity of the cavernous sinus, CSF, and carotid artery on the side contralateral to the lesion. RESULTS: Operative findings disclosed that 5 aneurysms were intradural and 6 were extradural. All except 2 were accurately assessed with CE 3D-CISS imaging. One intradural aneurysm adjacent to a large cavernous aneurysm and 1 cavernous giant aneurysm were assessed as partially intradural. On CE 3D-CISS images, the boundary between the CSF, cavernous sinus, and carotid artery was identified by high signal-intensity contrast in all cases. CONCLUSION: CE 3D-CISS MR imaging is useful for the differentiation between paraclinoid and cavernous sinus aneurysms.

Assessment of Vascular Supply of Hypervascular Extra-Axial Brain Tumors with 3T MR Regional Perfusion Imaging

BACKGROUND AND PURPOSE: The vascular supply of extra-axial brain tumors provided by the external carotid artery has not been studied with RPI. The purpose of this work was to determine whether RPI assessment is feasible and provides information on the vascular supply of hypervascular extra-axial brain tumors. MATERIALS AND METHODS: Conventional ASL and RPI studies were performed at 3T in 8 consecutive patients with meningioma. On the basis of MRA results, we performed RPI by placing a selective labeling slab over the external carotid artery. Five patients underwent DSA before surgery. Two neuroradiologists independently evaluated the overall image quality, the degree of tumor perfusion, and the extent of the tumor vascular territory on conventional ASL and RPI. RESULTS: In overall quality of conventional ASL and RPI, no images interfered with interpretation. In comparisons of the vascular tumor territory identified by the conventional ASL and RPI techniques, the territories coincided in 3 cases, were partially different in 4, and completely different in 1. The interobserver agreement was very good (κ = 0.82). In 5 patients who underwent DSA, the 4 patients in whom the dominant supply was the external carotid artery were scored as coincided or partially different. The 1 patient in whom the vascular supply was from the internal carotid artery was scored as completely different. CONCLUSIONS: RPI with selective labeling of the external carotid artery is feasible and may provide information about the vascular supply of hypervascular extra-axial brain tumors.

Quantitative evaluation of volatile hydrocarbons in post-mortem blood in forensic autopsy cases of fire-related deaths

Volatile hydrocarbons in post-mortem blood from victims of fires were analyzed quantitatively by headspace gas chromatography mass spectrometry. The benzene and styrene concentrations in the blood were positively correlated with the carboxyhemoglobin (CO-Hb) concentration, which is evidence that the deceased inhaled the hydrocarbons and carbon monoxide simultaneously. By contrast, the concentrations of toluene and CO-Hb in the blood were not significantly correlated. This lack of correlation could be explained by two different sources of toluene, with low blood concentrations of toluene arising when the deceased inhaled smoke and high blood concentrations of toluene arising when the deceased inhaled petroleum vapor or other unknown vapors. The quantity of soot deposited in the respiratory tract was classified into four grades (-, 1+, 2+, 3+). The mean CO-Hb concentration in the 1+ soot group was significantly lower than those in the 2+ (p<0.05) and 3+ (p<0.01) soot groups. The blood CO-Hb concentrations in the 1+ soot group were all below 30%. Those indicated that the deceased aspirated smoke that contained both soot and carbon monoxide. The wide variation in CO-Hb concentrations for each soot classification could be caused by the different types of smoke produced by different materials. For example, petroleum combustion with a limited supply of oxygen, like in a compartment fire, may produce a large volume of dense black smoke that contains a large quantity of soot. Soot deposits in the airways and the blood CO-Hb concentration are basic and essential autopsy findings that are used to investigate fire-related deaths. The quantitative GC-MS analysis of blood volatile hydrocarbons can provide additional useful information on the cause of the fire and the circumstances surrounding the death. In combination, these three findings are useful for the reconstruction of cases.

Metal preference of Zn(II) and Co(II) for the dinuclear metal binding site of IMP-1 metallo-β-lactamase and spectroscopic properties of Co(II)-substituted IMP-1 with mercaptoacetic acid

IMP-1 metallo-β-lactamase is a dinuclear Zn(II) enzyme that catalyzes the hydrolysis and inactivation of most β-lactams including carbapenems, and is involved in one of the mechanisms for generating clinical resistance to antibiotics in pathogenic bacteria. We investigated the metal preferences of Zn(II) and Co(II) for the apo-enzyme of IMP-1 metallo-β-lactamase, apo-IMP-1, which contains a dinuclear metal binding site (the Zn1 and Zn2 sites), by UV-visible spectroscopy. The UV-visible spectrum of apo-IMP-1 containing 1 equiv. of Co(II) and 1 equiv. of Zn(II) showed a high preference of Zn(II) for the Zn1 site compared to Co(II). Moreover, Zn(II) bound more strongly to the Zn2 site than Co(II). The interaction of IMP-1 metallo-β-lactamase with mercaptoacetic acid was also investigated using Co(II)-substituted IMP-1 and UV-visible spectroscopy. Possible metal binding modes of Co(II) or Zn(II) to the dinuclear metal binding site in apo-IMP-1 and of mercaptoacetic acid to Co(II)-substituted IMP-1 are proposed.

Detection of carbon monoxide poisoning that occurred before a house fire in three cases

In our institutes, we perform a quantitative evaluation of volatile hydrocarbons in post-mortem blood in all fatal fire-related cases using headspace gas chromatography mass spectrometry. We previously reported that benzene concentrations in the blood were positively correlated with carbon monoxide-hemoglobin (CO-Hb) concentrations in fire-related deaths. Here, we present 3 cases in which benzene concentrations in the blood were not correlated with CO-Hb concentrations. A high CO-Hb concentration without a hydrocarbon component, such as benzene, indicates that the deceased inhaled carbon monoxide that was not related to the smoke from the fire. Comparing volatile hydrocarbons with CO-Hb concentrations can provide more information about the circumstances surrounding fire-related deaths. We are currently convinced that this is the best method to detect if carbon monoxide poisoning occurred before a house fire started.

Single-chain variable fragment technology in forensic toxicological analysis: production of an antibody to fluvoxamine

Immunoassay techniques are widely used for drug screening in the fields of forensic toxicology and emergency medicine, because of their simple procedures and rapid outcome of results [1, 2]. To create an immunoassay method for a compound, the most laborious step is the production of an antibody that is specific to the compound. Here, we present a new recombinant antibody technology for producing a single-chain variable fragment (scFv). scFv is a small antibody molecule that retains high antigen specificity and binding activity of the original whole immunoglobulin [3]. One advantage of scFv is its simple production using bacterial cell cultures, which also provide variable functionalities by introducing mutations. Furthermore, creating scFv phage libraries, which display various scFvs, might be useful in searching for drug-reactive elements. This seems to be a powerful tool for rapid creation of new antidrug antibodies without immunizing animals. Recently, the frequency of psychotropic drug poisoning has increased in Japan [4]. Among such drugs, fluvoxamine (FLV), one of the selective serotonin reuptake inhibitor (SSRI) antidepressant drugs, is widely used for treatment of depression and obsessive compulsive disorders [5]. Although SSRIs are relatively safe as compared with conventional antidepressant drugs, such as tricyclic antidepressants and monoamine oxidase inhibitors [6], the number of FLV poisoning cases has increased according to the increase in its prescription [7, 8]. In this study, we created an anti-FLV scFv using novel recombinant antibody technology. FLV malate was obtained from Sigma-Aldrich (St. Louis, MO, USA). Mercaptosuccinyl bovine serum albumin (MS-BSA) was a generous gift from Prof. K. Fujiwara, Sojo University (Kumamoto, Japan). All other solvents and chemicals were of analytical grade, and purchased through local suppliers. BALB/c mice (female, 4 weeks old; Kyudo, Kumamoto, Japan) were maintained in the Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan, and were kept in an environmentally controlled room (22 ± 2 C, 50–70 % humidity, illuminated from 0700 to 1900 hours). All procedures were approved by the Kumamoto University Ethics Review Committee for Animal Experimentation. The immunogen (BSA–FLV) for induction of anti-FLV antibodies was prepared as described previously with a slight modification [9]. Briefly, FLV maleate (4.3 mg; approximately 10 lmol) in 1.0 ml of 50 mM phosphate buffer (pH 7.0) was mixed with N-[c-maleimidobutyryloxy] succinimide (GMBS) (0.25 mg; approximately 0.89 lmol), and incubated at room temperature with stirring. MS-BSA, estimated to contain 18 thiol groups per BSA molecule, was diluted with 3.0 ml of 0.1 M phosphate buffer (pH 7.0), and added immediately to the This article is for the special issue TIAFT2012 edited by Osamu Suzuki.