Successful selective production of vanillic acid from depolymerized sulfite lignin and its application to poly(ethylene vanillate) synthesis.

Towards lignin upgrading, vanillic acid (VA), a lignin-derived guaiacyl compound, was produced from sulfite lignin for successfully synthesizing poly(ethylene vanillate), an aromatic polymer. The engineered Sphingobium sp. SYK-6-based strain in which the genes responsible for VA/3-O-methyl gallic acid O-demethylase and syringic acid O-demethylase were disrupted was able to produce vanillic acid (VA) from the mixture consisting of acetovanillone, vanillin, VA, and other low-molecular-weight aromatics obtained by Cu(OH)2-catalyzed alkaline depolymerization of sulfite lignin and membrane fractionation. From the bio-based VA, methyl-4-(2-hydroxyethoxy)-3-methoxybenzoate was synthesized via methylesterification, hydroxyethylation, and distillation, and then it was subjected to polymerization catalyzed by titanium tetraisopropoxide. The molecular weight of the obtained poly(ethylene vanillate) was evaluated to be Mw = 13,000 (Mw/Mn = 1.99) and its melting point was 261 °C. The present work proved that poly(ethylene vanillate) is able to be synthesized using VA produced from lignin for the first time.

Antifungal activity of simply fractionated organosolv lignin against Trametes versicolor.

In an effort to achieve sustainable development goals, a reevaluation of the materials used in wooden buildings must be done, including the preservatives used to treat the materials. Since typical wood preservatives use toxic heavy metals, their handling and use can contaminate the environment. Therefore, substances such as lignin-derived components have been investigated as bio-based preservatives. Organosolv treatment is a promising technique for separating components of lignocellulosic biomass, which enables the utilization of each component. The present report describes components of lignocellulose with antifungal effects that were recovered after organosolv treatment using water and 1-butanol solvent at 473 K for 2 h, followed by simple solvent fractionation. The organosolv lignin was divided into three fractions: n-hexane soluble, ethyl acetate soluble, and ethyl acetate insoluble, yielding 23 wt%, 52 wt% and 13 wt%, respectively. Antifungal activity was determined using an agar plate method. White rot fungi (Trametes versicolor) was dispersed on the agar plate with a cellulose disc containing each lignin-derived fraction obtained from Japanese cedar. Results showed inhibition of fungal growth over the cellulose disc containing the n-hexane soluble fraction. To examine the effect in greater detail, the chemical structure of the n-hexane-soluble fraction on the antifungal activity was investigated. The content of phenolic hydroxyl group in n-hexane-soluble fraction was the highest (4.6 mmol/g), and the results from the chemical modification suggested that the functional group was required for antifungal action. In addition, the n-hexane-soluble fraction imparted some water resistance. The procedures used for cedar as a feedstock were applied to another type of biomass-bagasse-and its fractions showed antifungal activity similar to those of Japanese cedar.

Statistical parametric analysis of cerebral blood flow in vascular dementia with small-vessel disease using Tc-HMPAO SPECT.

BACKGROUND: Subcortical ischemic vascular dementia (SVD) caused by small-artery disease is a major cause of dementia. It still remains unclear, however, whether SVD may present with localized regional cerebral blood flow (rCBF) changes. We aimed to clarify the local rCBF changes associated with dementia in patients with early-stage SVD. METHODS: The subjects consisted of 15 patients with early-stage SVD [Mini Mental State Examination (MMSE) score: 20 +/- 3.5] without apparent brain atrophy (SVD group), 11 patients without dementia with white matter lesions (non-dementia-WML group) and 16 age-matched controls. All the subjects were right-handed and underwent brain perfusion single photon emission computed tomography (SPECT), magnetic resonance imaging and cognitive function testing. Statistical analysis of the differences in the SPECT rCBF was performed by SPM2. The degree of severity of the WMLs was evaluated based on the Scheltens rating scale. RESULTS: The results of SPM analysis revealed that the rCBF in the SVD group was significantly decreased in the pulvinar nuclei of the thalamus of both sides as compared with that in the controls, and in the left pulvinar nucleus as compared with that in the non-dementia-WML group. On the other hand, SPM analysis revealed no significant reduction in rCBF in the non-dementia-WML group as compared with that in the controls. The WMLs in the left parietal region were severer in the SVD group than in the non-dementia-WML group. CONCLUSIONS: In patients with early-stage SVD without apparent brain atrophy, significant rCBF reduction in the bilateral pulvinar nuclei as compared with that in normal controls, and in the left pulvinar nucleus as compared with that in patients without dementia with WMLs was found.

Clinical significance of cerebrovascular reserve in acetazolamide challenge -comparison with acetazolamide challenge H2O-PET and Gas-PET.

OBJECTIVE: The response of cerebral blood flow (CBF) to acetazolamide (ACZ) challenge is frequently determined in clinical settings to evaluate cerebrovascular reserve (CVR). A reduced CVR can indicate patients with occlusive cerebrovascular disease and compromised hemodynamics who may be at increased risk of cerebral ischemia. However, how precisely ACZ reflects cerebral hemodynamic impairment remains obscure. The present study aims to clarify the pathological significance of CVR in patients with occluded carotid arteries. METHODS: We recruited seventeen patients with occlusive lesions in the internal carotid artery (ICA) or middle cerebral artery (MCA). We assessed these patients in terms of resting cerebral blood flow (CBF) and the CVR response to ACZ challenge using H20 positron emission tomography (PET). In addition, we evaluated hemodynamic parameters including oxygen extraction fraction (OEF) using Gas-PET. RESULTS: We identified a significant negative correlation between the CVR and OEF or the cerebral blood volume (CBV)/CBF ratio, as a potential index of cerebral perfusion pressure. Although the CVR values were reduced in all regions with elevated OEF (Stage II), these values were highly variable regardless of the CBV/CBF ratios. The cut-off value of CVR alone could not detect Stage II, but when combined with resting CBF, misery perfusion accompanied by increased OEF was detected with high sensitivity (6/7) and specificity (61/62). CONCLUSION: CVR could be applied as an index reflecting both autoregulatory capacity and OEF. The present study also supported the notion that SPECT with ACZ challenge can be clinically applied to detect misery perfusion.

Spectral analysis of 99mTc-HMPAO for estimating cerebral blood flow: a comparison with H2(15)O PET.

Cerebral blood flow (CBF) can be quantified non-invasively using the brain perfusion index (BPI), which is determined using radionuclide angiographic data obtained through the use of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). The BPI is generally calculated using graphical analysis (GA). In this study, BPI was measured using spectral analysis (SA), and the usefulness of SA was compared with that of GA. Thirteen patients with various brain diseases and four healthy male volunteers were examined using radionuclide angiography with 99mTc-HMPAO. The BPI was measured for each subject using both SA and GA. In the four healthy volunteers, the BPI was examined at rest and after the intravenous administration of 1 g of acetazolamide (ACZ). An H2(15)O PET examination was also performed in the 13 patients; the BPIS and BPIG values were compared with the CBF measurements obtained using H2(15)O PET (CBFPET). The BPI values obtained by SA (BPIS) (x) and by GA (BPIG) (y) were correlated (y = 0.568x + 0.055, r = 0.901) in the 13 patients and four healthy volunteers at rest, although the BPIG values were underestimated by 36.1 +/- 7.5% (mean +/- SD) compared with the BPIS values. The degree of underestimation tended to increase with increasing BPIS values. The increase in the BPIS was 32.1 +/- 8.0% after the intravenous administration of ACZ, while the increase in BPIG was only 8.1 +/- 2.8%. This discrepancy was considered to be the result of the BPIG values being affected by the first-pass extraction fraction of the tracer. Although both BPIS and BPIG values were significantly correlated with the CBFPET values, the correlation coefficient for BPIS was higher than that for BPIG (BPIS: r = 0.881; BPIG: r = 0.832). These results suggest that SA produces a more reliable BPI for quantifying CBF using 99mTc-HMPAO than the conventional method using GA. The SA method should be especially useful for activation studies involving pharmacological intervention and/or clinical cases with an increased CBF.

Cerebral hemodynamics and metabolism in adult moyamoya disease: comparison of angiographic collateral circulation.

PURPOSE: The extent of the hemodynamic and metabolic impairments in adult patients with moyamoya disease is still controversial. The aim of the present study was to evaluate the hemodynamic and metabolic status in relation to the development of basal moyamoya vessels (BMVs). METHODS: The cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured using PET in ten patients with ischemic adult moyamoya disease (mean age, 36.6 years) and six age-matched normal controls (mean age, 33.3 years). The cerebrovascular reserve (CVR) after acetazolamide (ACZ) loading was also estimated using iodine-123 N-isopropyl-p-iodo amphetamine single photon emission computed tomography (123I-IMP SPECT). RESULTS: Based on the angiographic findings, eleven cerebral hemispheres with well-developed BMV (extensive BMV hemispheres) and nine cerebral hemispheres with diminished BMV (diminished BMV hemispheres) were identified. The main routes of collateral circulation in extensive BMV hemispheres were BMVs and leptomeningeal anastomoses. On the other hand, in diminished BMV hemispheres, transdural anastomosis was predominant, and leptomeningeal anastomoses were less developed. In cortices distal to the occluded internal carotid artery, the extensive BMV hemispheres exhibited a significantly lower CBF, CMRO2, CBF/CBV, and CVR (p < 0.05) and a significantly higher CBV and OEF than in diminished BMV hemispheres and controls (p < 0.05). Except for the CBF in the white matter, the mean hemodynamic and metabolic parameters of the diminished BMV hemispheres were not significantly different from those of the controls. CONCLUSION: The extensive development of basal moyamoya vessels is a sign of severe hemodynamic impairment in adult patients with ischemic moyamoya disease. The results may not apply to adults with hemorrhagic onset.

Cortical processing of tactile language in a postlingually deaf-blind subject.

We compared neural activation detected by magnetoencephalography (MEG) during tactile presentation of words and non-words in a postlingually deaf-blind subject and six normal volunteers. The left postcentral gyrus, bilateral inferior frontal gyri, left posterior temporal lobe, right anterior temporal lobe, bilateral middle occipital gyri were activated when tactile words were presented to the right hand of the deaf-blind subject. This set of activated regions was not observed in the normal volunteers, although activation of several combinations of these regions was detected. Positron emission tomography confirmed the location of the MEG-activated areas in the deaf-blind subject. Our results demonstrated that the deaf-blind subject is heavily involved in interpreting tactile language by enhancing cortical activation of cognitive and semantic processing.

Cerebral and cerebellar activation in power and precision grip movements: an H2 15O positron emission tomography study.

SUMMARY: Most human manual grip movements can be divided into power gripping and precision gripping, but central neural control during these tasks remains unclear. We investigated activation of the whole brain to analyze how simple hand movements are performed. The cerebral blood flow of seven healthy right-handed volunteers was measured by H2 15O positron emission tomography during right grip tasks without gripping a target object. Auditory-cued, repetitive power grips (i.e., fist making) and repetitive precision grips (i.e., opposition of the tip of the index finger and the tip of the thumb) were performed at 1.26 Hz. The areas activated during both tasks were the left primary sensorimotor cortex, caudal portion of the dorsal premotor, caudal portion of the supplementary motor area, cingulate motor area, and the right spinocerebellum and intermediate region of the cerebrocerebellum in comparison with the rest state. The analysis of power grip-precision grip tasks showed the activated peaks in the upper portion of the left sensorimotor area and right cerebellar vermis, but these areas were activated in both the tasks [(power grip-rest) and (precision grip-rest)] with uncorrected P < 0.001 as the statistical criterion. With P < 0.05 corrected as the statistical criterion, the results showed no significant activated peaks in regional cerebral blood flow. Our findings indicate no difference in brain activation between the acts of power grip and precision grip without a target object.

Heterogeneity of cerebral blood flow in Alzheimer disease and vascular dementia.

BACKGROUND AND PURPOSE: Alzheimer disease (AD) and vascular dementia (VaD) are the two major diseases that cause dementia, and early diagnosis is important. Single photon emission CT (SPECT) of cerebral blood flow (CBF) is used for the early detection of dementia and as an auxiliary method for follow-up. AD shows reduced posterior blood flow and VaD manifests reduced anterior blood flow on CBF SPECT images. We examined the usefulness of 3D fractal analysis of CBF SPECT images to objectively quantify the heterogeneity of CBF in patients with AD and VaD. METHODS: Thirty-two patients with AD and 22 with VaD based on neuropsychologic tests and imaging findings, as well as 20 age-matched control subjects underwent technetium-99m hexamethyl propyleneamine oxime CBF SPECT. We then conducted statistical image processing by 3D fractal analysis on reconstructed data. Fractal dimension, an index of heterogeneity, was then calculated for the whole brain, as well as for the anterior and posterior regions of the brain. A higher fractal dimension indicates that the CBF SPECT image is uneven. The ratio of fractal dimension of the anterior region to fractal dimension of the posterior region (A/P ratio) was calculated. Heterogeneity of CBF was compared among the AD, VaD, and control groups. RESULTS: Fractal dimensions of the AD, VaD, and control groups were 1.072+/-0.179 (mean +/- SD), 1.005+/-0.156, and 0.806+/-0.06, respectively. A significant difference of fractal dimension was noted between the control group and the two types of dementia (P<.0001); however, no significant difference was noted between the AD and VaD groups. The A/P ratios of the AD and VaD groups were significantly different (0.952 and 1.163, respectively; P<.01). CONCLUSION: Analysis of CBF SPECT images quantitatively showed that the fractal dimension was significantly higher (indicating heterogeneity) in patients with AD and VaD when compared with age-matched control subjects. Comparison of the A/P ratio on CBF SPECT images between AD and VaD groups showed that the heterogeneity of CBF was posterior-dominant for AD and anterior-dominant for VaD. Thus, 3D fractal analysis enabled a simple and objective evaluation of the heterogeneity of CBF in patients with AD and VaD.

Interobserver variability of cerebral blood flow measurements obtained using spectral analysis and technetium-99m labeled compounds.

Radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or technetium-99m ethyl cysteinate dimer (99mTc-ECD) enables the non-invasive estimation of absolute cerebral blood flow (CBF) to be determined by using spectral analysis (SA). We previously demonstrated the clinical use of SA; however, this method involves a few manual steps. The aim of this study was to evaluate the interobserver variability of CBF estimations made using SA and compare these results with those obtained by using graphical analysis (GA). In twenty patients with various brain diseases (27-74 years old), radionuclide angiography examinations were performed using 99mTc-labeled compounds (10 patients, 99mTc-HMPAO; 10 patients, 99mTc-ECD). Bilateral cerebral hemispheres were studied in all patients, and the brain perfusion index (BPI) values were estimated using SA and GA. The interobserver variability between two observers was then assessed. A good correlation between the BPI values assessed using both SA (BPI(S)) and GA (BPI(G)) was obtained. The correlation coefficient for BPI(S) (r = 0.987) was almost the same as that for BPI(G) (r = 0.982). The degree of interobserver variability was not affected by the measurement of elevated BPI values. Measurements carried out by two observers using both SA and GA exhibited a similar degree of interobserver variability. SA appears to have a satisfactory interobserver variability and may be more suitable for clinical applications.

Statistical image analysis of cerebral blood flow in vascular dementia with small-vessel disease.

UNLABELLED: Small-vessel disease with dementia, which is the most frequent type of vascular dementia (VaD), often shows a cerebral blood flow (CBF) distribution with no obvious focal abnormalities and is therefore difficult to evaluate objectively. In this study, we combined CBF SPECT with 3-dimensional fractal analysis (3D-FA) to quantitatively assess the heterogeneity of CBF distribution and with 3-dimensional stereotactic surface projections (3D-SSP) to evaluate the distribution of CBF. We then evaluated the clinical validity of these techniques for the imaging diagnosis of VaD. METHODS: The subjects consisted of 17 patients who were diagnosed as having VaD due to small-vessel disease (VaD group) on the basis of a full clinical examination, including history, neuropsychologic tests, neurologic examination, and neuroimaging methods, and 20 healthy volunteers (control group). CBF SPECT was performed with (99m)Tc-hexamethylpropyleneamine oxime, and the reconstructed images were subjected to image processing by 3D-FA and 3D-SSP. Based on the results, the fractal dimension (FD) was compared between the VaD and control groups, and the distribution pattern of CBF was examined in the VaD group. RESULTS: The mean FD values in the VaD group and the control group were 1.093 +/- 0.153 and 0.853 +/- 0.062 (mean +/- SD), respectively. The mean FD value in the VaD group was significantly higher than that in the control group (P < 0.0001). 3D-SSP analysis in the VaD group showed that there were 2 abnormal patterns: One was globally reduced blood flow in the whole cerebral cortex, and the other was a reduction mainly confined to the frontal region. CONCLUSION: CBF SPECT images showed higher mean FD values in the VaD group than in the control group, suggesting a difference in the heterogeneity of CBF. Image processing with 3D-SSP successfully revealed that reduced cortical blood flow could be divided into 2 patterns. Because image analysis techniques, such as 3D-FA and 3D-SSP, allowed the simple and objective evaluation of CBF in patients with VaD, these methods seem to be useful for detailed examination of the blood flow pattern detected by CBF SPECT in patients with VaD.

Quantification of the heterogeneity of cerebral blood flow in vascular dementia.

BACKGROUND: In vascular dementia (VaD), assessment of cerebral blood flow by single photon emission computed tomography (CBF SPECT) has been used to detect a patchy decrease of blood flow or a frontal reduction. In addition to reduced blood flow, the heterogeneous distribution of cerebral blood flow is often observed in VaD. However, no objective method to evaluate the heterogeneity has been established. In this study, we applied three-dimensional fractal analysis (3D-FA) to CBF SPECT images as a method for assessing the heterogeneity of the cerebral blood flow distribution in VaD. SUBJECTS AND METHODS: The subjects included 18 patients with a diagnosis of VaD (aged 69.7 +/- 8.3) based on neuropsychological testing and imaging findings and 18 age-matched controls (aged 66.9 +/- 10.3). CBF SPECT images were obtained with (99m)Tc-hexamethyl propyleneamine oxime. On the reconstructed images, we obtained a linear regression equation between the cut-off values (from 35 to 50 %) and the number of voxels with a radioactivity exceeding the cut-off value transformed into natural logarithms, and then calculated the fractal dimension from the slope of the regression line thus obtained. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. RESULTS: The fractal dimensions were 1.084 +/- 0.153 and 0.853 +/- 0.062 (mean +/- SD) in the VaD and control groups, respectively. The fractal dimension was significantly greater in the VaD group than in the control group (p < 0.0001). A significant negative correlation was observed between the fractal dimension and the MMSE score in the VaD group (r = 0.871, p < 0.0001). CONCLUSIONS: Because the CBF SPECT images of VaD patients showed a higher fractal dimension, these images were quantitatively more heterogeneous than those of age-matched controls. In the VaD group, cognitive function was shown to decline as the fractal dimension increased and images became more heterogeneous.

Automatic determination of brain perfusion index for measurement of cerebral blood flow using spectral analysis and 99mTc-HMPAO.

Cerebral blood flow (CBF) can be non-invasively quantified using the brain perfusion index (BPI), determined from radionuclide angiographic data generated by technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO). We previously reported the use of a spectral analysis (SA) method using (99m)Tc-HMPAO to calculate the BPI. In this report, we demonstrate an automatic method for determining the optimal BPI value and compare the optimal BPI values with the absolute CBF values measured using H(2)(15)O positron emission tomography (PET). Bilateral cerebral hemispheres of 11 patients with various brain diseases were examined using (99m)Tc-HMPAO. In the automatic SA procedure, the radioactivity curve for the aortic arch ( C (a)) was shifted by 0-10 s. The radioactivity curve for the brain ( C (b)) was estimated using the shifted C (a), and the error value between the actually measured and the estimated C (b) (Err) was calculated. When the Err was at a minimum, the BPI value was defined as optimal BPI. The difference in BPI from the optimal BPI was calculated as |BPI - optimal BPI| / optimal BPIx100 (%). In all participants, an H(2)(15)O PET examination was also performed, and the BPI values were compared with the absolute CBF values measured using H(2)(15)O PET (mCBF(PET)). The difference between BPI and the optimal BPI increased significantly from 4.87%+/-1.69% to 18.38%+/-3.93% (mean+/-SD) when the Err value increased. The optimal BPI value ( y) was well correlated with the mCBF(PET) value ( x) ( y=0.21 x-0.0075, r=0.800). Our results suggest that this automatic SA method provides an accurate estimate of BPI that can be used for the quantification of CBF using (99m)Tc-HMPAO SA.

Detection of misery perfusion with split-dose 123I-iodoamphetamine single-photon emission computed tomography in patients with carotid occlusive diseases.

BACKGROUND AND PURPOSE: Patients with carotid occlusive disease and stage 2 cerebral hemodynamic failure, characterized by an increased oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) and otherwise known as misery perfusion, have a high risk of cerebral ischemia and subsequent stroke. In clinical practice, the detection of patients with misery perfusion through the use of widely available, noninvasive, and cost-effective modalities such as single-photon emission computed tomography (SPECT) is extremely important. METHODS: We evaluated the relationships between the regional hemodynamic status of cerebral circulation, measured with split-dose [123I] N-isopropyl-p-iodoamphetamine SPECT (123I-IMP SPECT) and an acetazolamide challenge, and hemodynamic parameters, including OEF measured with PET, in 27 patients with both unilateral and bilateral carotid occlusive diseases. RESULTS: A significant negative correlation was found between the SPECT-measured cerebrovascular reserve after acetazolamide administration and both the PET-measured OEF and cerebral blood volume. Neither the cerebrovascular reserve nor the cerebral blood flow index, when expressed as a SPECT-measured cerebrum-to-cerebellum ratio, was useful for detecting lesions with an elevated OEF. However, a combination of the cerebrovascular reserve and cerebral blood flow index showed high sensitivity, specificity, and positive predictive value for the detection of misery perfusion. CONCLUSIONS: Our study suggests that split-dose 123I-IMP SPECT with an acetazolamide challenge could be useful for screening patients with misery perfusion in carotid occlusive diseases.

Assessment of acetazolamide reactivity in cerebral blood flow using spectral analysis and technetium-99m hexamethylpropylene amine oxime.

Cerebral blood flow (CBF) can be quantified noninvasively using the brain perfusion index (BPI), determined from radionuclide angiographic data generated with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). Previously, the BPI has been calculated using graphical analysis (GA); however, the GA method is greatly affected by the first-pass extraction fraction and retention fraction, which are not only variable, but lower in cases with an increased CBF, such as after the administration of acetazolamide. Thus, GA-calculated BPI values (BPIG) may not reflect the absolute CBF. The objective of this study was to use the spectral analysis of radionuclide angiographic data collected using 99mTc-HMPAO to examine changes in the BPI after the administration of acetazolamide. We studied the CBF of both cerebral hemispheres in six healthy male volunteers; the BPI was measured at rest and after the intravenous administration of 1 g of acetazolamide. In all participants, an H215O positron emission tomography (PET) examination was also performed, and the spectral analysis-calculated BPI values (BPIS) and BPIG values were compared with the actual CBF measured using H215O PET (mCBFPET). The BPIS was 1.070 +/- 0.051 (mean +/- SD) at rest and 1.497 +/- 0.098 after acetazolamide; the corresponding BPIG values were 0.646 +/- 0.073 and 0.721 +/- 0.107. The BPIS values were significantly correlated with the mCBFPET values, whereas the BPIG values were not. According to the BPIS values, the increase in BPI after the intravenous administration of acetazolamide was 40.1 +/- 8.4%, as opposed to an increase of only 11.3 +/- 6.5% according to the BPIG values. These results suggest that the spectral analysis of 99mTc-HMPAO-generated data yields a more reliable BPI than GA for the quantification of CBF after acetazolamide administration.