Evaluation of elastin fibres in young and aged eyelids and abdominal skin using computational 3D structural analysis.

Background: Aging-related degeneration of elastic fibres causes skin wrinkles and loss of elasticity. A correlation has been reported between dermal elastic fibre degradation and wrinkles. However, the mechanism of wrinkle formation is complex and unclear. To establish methods for treating wrinkles, it is necessary to understand the aging-related morphological alterations underlying elastin fibre degradation or disappearance. Objectives: To image and analyse aging-related three-dimensional (3D) morphological alterations of elastic fibres in the eyelid and abdominal skin. Methods: Excised human eyelid and abdominal skin tissues were examined. The structure of elastic fibres in the skin tissues was examined via nuclear, tropoelastin and fibrillin-1 immunostaining. Then, 3D imaging was performed using a confocal laser microscope and tissue decolourization technology. Images were analysed using a computational method. Results: The decolourization technology made it possible to image elastin fibres in 3D, and we devised a method for analyzing the elastin fibre structure using computational methods. It was quantitatively shown that the eyelid skin has a more complex fibrous structure than the abdomen, and the fibres became curved, shortened and thickened with age. Conclusions: We provide a novel 3D analysis method for elastin fibres and report age-related alterations in elastin fibre structure in the human eyelid and abdominal skin. This method contributes to the understanding of elastin fibre degeneration in more detail than conventional methods. Applying this 3D analysis method to skin tissues will contribute to a better understanding of age-related changes in fibres and to the development of novel wrinkle treatments.

Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma.

Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA. We further identified VAV1 mutations and a new translocation, VAV1-STAP2, in seven of the 85 RHOA mutation-negative samples (8.2%), whereas none of the 41 RHOA mutation-positive samples exhibited VAV1 mutations. Augmentation of 174Tyr phosphorylation was also demonstrated in VAV1-STAP2. Dasatinib, a multikinase inhibitor, efficiently blocked the accelerated VAV1 phosphorylation and the associating TCR signaling by both G17V RHOA and VAV1-STAP2 expression. Phospho-VAV1 staining was demonstrated in the clinical specimens harboring G17V RHOA and VAV1 mutations at a higher frequency than those without. Our findings indicate that the G17V RHOA-VAV1 axis may provide a new therapeutic target in AITL.

Pituitary Macroadenoma and Visual Impairment: Postoperative Outcome Prediction with Contrast-Enhanced FIESTA.

BACKGROUND AND PURPOSE: Contrast-enhanced FIESTA can depict anterior optic pathways in patients with large suprasellar tumors. We assessed whether the degree of kink in the optic nerve at the optic canal orifice on contrast-enhanced FIESTA correlates with the postoperative improvement of visual impairment in patients with pituitary macroadenoma. MATERIALS AND METHODS: Thirty-one patients with pituitary macroadenoma who underwent preoperative MR imaging and an operation were evaluated. We measured the optic nerve kinking angle on sagittal oblique contrast-enhanced FIESTA parallel to the optic nerve; the optic nerve kinking angle was defined as the angle between a line parallel to the planum sphenoidale and a line parallel to the intracranial optic nerve at the optic canal orifice. We used logistic regression analyses to determine whether the clinical (sex, age, and duration of symptoms) and imaging (tumor height, chiasmal compression severity, hyperintense optic nerve on T2WI, and optic nerve kinking angle) characteristics were associated with the postoperative improvement (good-versus-little improvement) of visual acuity disturbance and visual field defect. RESULTS: There were 53 impaired sides before the operation: 2 sides with visual acuity disturbance alone, 25 with visual field defect alone, and 26 with both. After the operation, good improvement was found in 17 of the 28 sides with visual acuity disturbance and in 32 of the 51 sides with visual field defects. Only the optic nerve kinking angle was significantly associated with good improvement of the visual acuity disturbance (P = .011) and visual field defect (P = .002). CONCLUSIONS: The degree of the optic nerve kinking angle was an independent predictor of postoperative improvement, indicating that irreversible damage to the optic nerve may be associated with its kinking at the optic canal orifice.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds.

Tumor consistency of pituitary macroadenomas: predictive analysis on the basis of imaging features with contrast-enhanced 3D FIESTA at 3T.

BACKGROUND AND PURPOSE: Preoperative evaluation of pituitary macroadenoma tumor consistency is important for neurosurgery. Thus, we aimed to retrospectively assess the role of contrast-enhanced FIESTA in predicting the tumor consistency of pituitary macroadenomas. MATERIALS AND METHODS: Twenty-nine patients with pituitary macroadenomas underwent conventional MR imaging sequences and contrast-enhanced FIESTA before surgery. Two neuroradiologists assessed the contrast-enhanced FIESTA, contrast-enhanced T1WI, and T2WI. On the basis of surgical findings, the macroadenomas were classified by the neurosurgeons as either soft or hard. Finally, Fisher exact probability tests and unpaired t tests were used to compare predictions on the basis of the MR imaging findings with the tumor consistency, collagen content, and postoperative tumor size. RESULTS: The 29 pituitary macroadenomas were classified as either solid or mosaic types. Solid type was characterized by a homogeneous pattern of tumor signal intensity without intratumoral hyperintense dots, whereas the mosaic type was characterized by many intratumoral hyperintense dots on each MR image. Statistical analyses revealed a significant correlation between tumor consistency and contrast-enhanced FIESTA findings. Sensitivity and specificity were higher for contrast-enhanced FIESTA (1.00 and 0.88-0.92, respectively) than for contrast-enhanced T1WI (0.80 and 0.25-0.33, respectively) and T2WI (0.60 and 0.38-0.54, respectively). Compared with mosaic-type adenomas, solid-type adenomas tended to have a hard tumor consistency as well as a significantly higher collagen content and lower postoperative tumor size. CONCLUSIONS: Contrast-enhanced FIESTA may provide preoperative information regarding the consistency of macroadenomas that appears to be related to the tumor collagen content.

Levels of the oxidative stress marker γ-glutamyltranspeptidase at different stages of nonalcoholic fatty liver disease.

OBJECTIVES: This study investigated oxidative stress in the liver, by determining hepatic expression and serum levels of γ-glutamyltranspeptidase (GGT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in different stages of nonalcoholic fatty liver disease (NAFLD), and assessed whether GGT can differentiate between the various stages of NAFLD. METHODS: Expression of GGT and 8-OHdG was examined in biopsy specimens by immunohistochemistry, and serum GGT and 8-OHdG levels were measured by enzyme-linked immuno sorbent assays in patients with simple fatty liver (n = 10), nonalcoholic steatohepatitis (NASH; n = 10) and, as a control, in alcoholic liver disease (ALD; n = 10). RESULTS: Hepatic tissue expression of GGT and 8-OHdG was seen in ALD, NASH and fatty liver patients. The percentage of hepatocytes positive for 8-OHdG expression and serum 8-OHdG levels was significantly higher in patients with NASH than simple fatty liver. Serum GGT levels were increased in all cases with ALD, NASH and fatty liver, and correlated significantly with serum levels of 8-OHdG in ALD and NASH, but not in simple fatty liver. CONCLUSIONS: Levels of GGT in fatty liver patients may compensate for mild oxidative stress by repressing 8-OHdG levels and preventing progression to NASH; however further oxidative stress leads to increased levels of 8-OHdG and the development of NASH.

The application of atelocollagen gel in combination with porous scaffolds for cartilage tissue engineering and its suitable conditions.

For improving the quality of tissue-engineered cartilage, we examined the in vivo usefulness of porous bodies as scaffolds combined with an atelocollagen hydrogel, and investigated the suitable conditions for atelocollagen and seeding cells within the engineered tissues. We made tissue-engineered constructs using a collagen sponge (CS) or porous poly(L-lactide) (PLLA) with human chondrocytes and 1% hydrogel, the concentration of which maximized the accumulation of cartilage matrices. The CS was soft with a Young's modulus of less than 1 MPa, whereas the porous PLLA was very rigid with a Young's modulus of 10 MPa. Although the constructs with the CS shrank to 50% in size after a 2-month subcutaneous transplantation in nude mice, the PLLA constructs maintained their original sizes. Both of the porous scaffolds contained some cartilage regeneration in the presence of the chondrocytes and hydrogel, but the PLLA counterpart significantly accumulated abundant matrices in vivo. Regarding the conditions of the chondrocytes, the cartilage regeneration was improved in inverse proportion to the passage numbers among passages 3-8, and was linear with the cell densities (10(6) to 10(8) cells/mL). Thus, the rigid porous scaffold can maintain the size of the tissue-engineered cartilage and realize fair cartilage regeneration in vivo when combined with 1% atelocollagen and some conditioned chondrocytes.

Involvement of fibroblast growth factor 18 in dedifferentiation of cultured human chondrocytes.

OBJECTIVE: Chondrocytes inevitably decrease production of cartilaginous matrices during long-term cultures with repeated passaging; this is termed dedifferentiation. To learn more concerning prevention of dedifferentiation, we have focused here on the fibroblast growth factor (FGF) family that influences chondrocyte proliferation or differentiation. MATERIALS AND METHODS: We have compared gene expression between differentiated cells in passage 3 (P3) and dedifferentiated ones in P8 of human cultured chondrocytes. We also performed ligand administration of the responsive factor or its gene silencing, using small interfering RNA (siRNA). RESULTS: FGFs 1, 5, 10, 13 and 18 were higher at P8 compared to P3, while FGFs 9 and 14 were lower. Especially, FGF18 showed a 10-fold increase by P8. Ligand administration of FGF18 in the P3 cells, or its gene silencing using siRNA in the P8 cells, revealed dose-dependent increase and decrease respectively in type II collagen/type I collagen ratio. Exogenous FGF18 also upregulated expression of transforming growth factor beta (TGF-beta), the anabolic factor of chondrocytes, in P3 chondrocytes, but P8 cells maintained a low level of TGF-beta expression, suggesting a decrease in responsiveness of TGF-beta to FGF18 stimulation in the dedifferentiated chondrocytes. CONCLUSION: FGF18 seems to play a role in maintenance of chondrocyte properties, although its expression was rather high in dedifferentiated chondrocytes. Upregulation of FGF18 in dedifferentiated chondrocytes implied that it may be a marker of dedifferentiation.

Physiological uptake of 18F-fluorodeoxyglucose in uterine endometrium and myometrium: correlation with uterine motility evaluated by cine magnetic resonance imaging.

BACKGROUND: Accumulation of (18)F-fluorodeoxyglucose ((18)F-FDG) in the uterine endometrium and uterine motility are dependent on menstrual cycle. However, the relationship between them remains unknown. PURPOSE: To investigate the relationship between radiometabolic activity of (18)F-FDG in the uterus and uterine motility observed by cine magnetic resonance imaging (MRI). MATERIAL AND METHODS: The study population consisted of 65 healthy, fertile women, selected from 229 women who underwent positron emission tomography (PET), computed tomography (CT), and MRI for cancer screening at our facility. They were divided into three groups according to their menstrual cycle phases: menstrual, follicular-periovulatory, and luteal. Regions of interest (ROIs) were placed over the endometrium and myometrium to calculate the standardized uptake value (SUV). Uterine peristalsis and contraction shown by cine MR imaging were evaluated visually, and the correlation between FDG uptake and uterine movements was assessed. RESULTS: After excluding nine patients due to inadequate images, 56 patients (19 follicular-periovulatory, 27 luteal, and 10 menstrual) were analyzed. FDG uptake of the endometrium, frequency of peristalsis, and the presence of sustained contraction varied according to the menstruation cycle, with a tendency toward greater uptake in the menstrual phase, but there was little relationship between the frequency of uterine peristalsis and FDG accumulation in the uterus. Significantly higher FDG accumulation in the endometrium was observed in patients with sustained contractions (3.32+/-1.47) than in those without contractions (2.45+/-0.66). CONCLUSION: Our preliminary data suggest that FDG accumulation in the endometrium tends to be higher in patients with uterine contraction, although there was no significant correlation between uterine peristalsis and FDG uptake in the uterine myometrium or endometrium.

Chronic osmotic stimuli increase salusin-beta-like immunoreactivity in the rat hypothalamo-neurohypophyseal system: possible involvement of salusin-beta on [Ca2+]i increase and neurohypophyseal hormone release from the axon terminals.

Salusin-alpha and -beta were recently discovered as bioactive endogenous peptides. In the present study, we investigated the effects of chronic osmotic stimuli on salusin-beta-like immunoreactivity (LI) in the rat hypothalamo-neurohypophyseal system. We examined the effects of salusin-beta on synaptic inputs to the rat magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and neurohypophyseal hormone release from both freshly dissociated SONs and neurohypophyses in rats. Immunohistochemical studies revealed that salusin-beta-LI neurones and fibres were markedly increased in the SON and the magnocellular division of the paraventricular nucleus after chronic osmotic stimuli resulting from salt loading for 5 days and dehydration for 3 days. Salusin-beta-LI fibres and varicosities in the internal zone of the median eminence and the neurohypophysis were also increased after osmotic stimuli. Whole-cell patch-clamp recordings from rat SON slice preparations showed that salusin-beta did not cause significant changes in the excitatory and inhibitory postsynaptic currents of the MNCs. In vitro hormone release studies showed that salusin-beta evoked both arginine vasopressin (AVP) and oxytocin release from the neurohypophysis, but not the SON. In our hands, in the neurohypophysis, a significant release of AVP and oxytocin was observed only at concentrations from 100 nm and above of salusin-beta. Low concentrations below 100 nm were ineffective both on AVP and oxytocin release. We also measured intracellular calcium ([Ca(2+)](i)) increase induced by salusin-beta on freshly-isolated single nerve terminals from the neurohypophysis devoid of pars intermedia. Furthermore, this salusin-beta-induced [Ca(2+)](i) increase was blocked in the presence of high voltage activated Ca(2+)channel blockers. Our results suggest that salusin-beta may be involved in the regulation of body fluid balance by stimulating neurohypophyseal hormone release from nerve endings by an autocrine/paracrine mechanism.

The cytoplasmic male-sterile type and normal type mitochondrial genomes of sugar beet share the same complement of genes of known function but differ in the content of expressed ORFs.

The complete nucleotide sequence (501,020 bp) of the mitochondrial genome from cytoplasmic male-sterile (CMS) sugar beet was determined. This enabled us to compare the sequence with that previously published for the mitochondrial genome of normal, male-fertile sugar beet. The comparison revealed that the two genomes have the same complement of genes of known function. The rRNA and tRNA genes encoded in the CMS mitochondrial genome share 100% sequence identity with their respective counterparts in the normal genome. We found a total of 24 single nucleotide substitutions in 11 protein genes encoded by the CMS mitochondrial genome. However, none of these seems to be responsible for male sterility. In addition, several other ORFs were found to be actively transcribed in sugar beet mitochondria. Among these, Norf246 was observed to be present in the normal mitochondrial genome but absent from the CMS genome. However, it seems unlikely that the loss of Norf246 is causally related to the expression of CMS, because previous studies on mitochondrial translation products failed to detect the product of this ORF. Conversely, the CMS genome contains four transcribed ORFs (Satp6presequence, Scox2-2 , Sorf324 and Sorf119) which are missing from the normal genome. These ORFs, which are potential candidates for CMS genes, were shown to be generated by mitochondrial genome rearrangements.

Neural activity of the globus pallidus interna and its anatomical relations to the optic tract in Parkinson's disease.

BACKGROUND: To reveal landmarks for placing the globus pallidus interna (GPi) target on MR images, visual evoked potentials (VEPs) of the optic tract (OT) and neural activities of the GPi were studied retrospectively. METHODS: The dorsal and lateral border of the OT were determined by VEPs of the OT, and neural activity in the pallidal region was recorded with a semimicro-electrode in 20 patients. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess the condition of each patient before and 6 months and 12 months after surgery. FINDINGS: The location of trajectories relative to the lateral border of the OT were 3 mm medial (-3) in 6, 2 mm medial (-2) in 7, 1 mm medial (-1) in 8, at the lateral border (0) in 6, 1 mm lateral (+1) in 5, 2 mm lateral (+2) in 6, and 3 mm lateral (+3) in 5. The mean amplitudes along trajectories -3 and -2 mm were significantly higher than the others (post-hoc, p<0.01). In dorsoventral relations, the amplitudes from 5.1 mm to 6.8 mm of the medial trajectories (-3 to 0 mm) were significantly higher than others (post-hoc, p<0.01). The lesions placed medial to the lateral border of the OT located just above the lateral border of the OT on postoperative MR images (n=12) and brought better surgical benefits of total motor score, rigidity and bradykinesia than those placed lateral to the OT (n=8). INTERPRETATION: Our data indicate that hyperactive cells of the GPi are located medial to the lateral border of the OT and at least 5.1 mm above its dorsal surface, and this corresponds to the area just above the lateral border of the OT on MR images.

Age-related pattern of body density and body composition in Japanese males and females, 11 and 18 years of age.

The age-related pattern of body density and body composition in Japanese males (n = 266) and females (n = 318), 11.00 to 18.99 years of age was studied. Body density (BD) as well as height, body weight, and seven skinfold thicknesses were measured. Percentage fat (%Fat) was calculated using the age- and sex-specific equation of Lohman. Fat mass (FM), fat-free mass (FFM), and the body mass index (BMI) were calculated. The trend for BD in males was lowest at 11 years (1.0530 g/ml) and increased to 1.0695 g/ml at 14 years, and then decreased slightly at 15 to 17 years. In female, BD decreased from 1.0530 g/ml at 13 years to 1.0424 g/ml at 17 years. Mean %Fat was highest in males at 11 years (15.8%), and lowest at 14 years (10.1%). The highest mean %Fat in females occurred at 16 years (22.8%), and the lowest at age 11 years (15.2%). Overall, only 6.8% of males and 3.1% of females were classified as obese. Between 11 and 18 years, FFM of males differed by 20.7 kg or 67.9%, whereas females showed a difference of only 10.8 kg or 34.7%. Consequently, age effects explained approximately 60% of the male variance of FFM but only 26% in females. Body density of each sex and age group in this study did not differ significantly from previous Japanese studies, and the pooled BD data for 1,457 Japanese including the present study are reported as a reference.

The sugar beet mitochondrial nad4 gene: an intron loss and its phylogenetic implication in the Caryophyllales.

The sugar beet mitochondrial gene for subunit IV of NADH dehydrogenase ( nad4) has been characterized. Unlike the corresponding genes in wheat and turnip, sugar beet nad4 lacks the second intron ( nad4-i2). Northern-blot analysis demonstrates transcription of the gene. A total of 19 RNA editing sites were identified in the sugar beet nad4 transcripts; interestingly, there is no editing in the region which flanks the lost intron. This observation is in favour of intron loss via homologous recombination of an edited RNA intermediate. We also found that the nad4-i2 intron is absent from the mitochondrial genomes of all examined members of the Caryophyllales, but present in the closely related orders, Polygonales and Plumbaginales, which suggests that the intron was lost in the common ancestor of the Caryophyllales.

Significance of absent prohormone convertase 1/3 in inducing clinically silent corticotroph pituitary adenoma of subtype I--immunohistochemical study.

Biologically inactive ACTH-producing pituitary adenoma is known as clinically silent corticotroph adenoma. To search for the mechanism causing clinically silent corticotroph adenoma, we immunohistochemically examined the expression of prohormone convertase 1/3 (PC1/3) in this type of adenoma and compared our results with those obtained for Cushing's disease. All of the Cushing's disease specimens exhibited strongly positive PC1/3 exhibition. On the contrary, the expression of PC1/3 was very weak in the clinically silent corticotroph adenoma specimens. The absence of PC1/3 in clinically silent corticotroph adenoma indicates that silent corticotroph adenomas arise in a different cell type sharing the prohormone pro-opiomelanocortin (POMC), but processing it differently, accounting for the lack of clinical symptoms due to ACTH excess.

Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure.

UNLABELLED: [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. METHODS: Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. RESULTS: The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3 +/- 0.2 and 5.0 +/- 0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p < 0.05). Although no systematic deviations were noted in K*1 or rCMRglc, there were small deviations in K* (less than 10%) and LC (less than 5%) with a statistical significance (p < 0.01). CONCLUSION: The deviation between the measurements in K* and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constraints can be used to estimate rCMRglc and LC sequentially in a single PET scanning session.

Assessment of cerebral hemodynamics before and after revascularization in patients with occlusive cerebrovascular disease by means of quantitative IMP-SPECT with double-injection protocol.

UNLABELLED: The purpose of this study was to validate a double-injection (DI) method with N-isopropyl-[123I]p-iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) twice in a single session of dynamic SPECT and to elucidate a possible role of this method to identify patients with occlusive disease of major cerebral arteries, who might benefit from cerebral revascularization procedures (CR). MATERIALS AND METHODS: Fourteen patients with occlusion or severe stenosis of the internal carotid or middle cerebral artery were studied before and after CR to assess hemodynamic changes after revascularization treatment. We quantitatively measured rCBF before and after acetazolamide (ACZ) challenge along with cerebrovascular reserve capacity (CVR) with two injections of IMP in a single session of dynamic SPECT scans (DI method). The reliability and reproducibility of the DI method were validated by means of a simulation study and in eight patients who were examined without ACZ challenge to measure baseline rCBF twice. RESULTS: The analysis of simulated noisy data with realistic noise levels showed that the errors of the estimates for the first and the second rCBF and for the increase in rCBF were 2.6%, 8.1% and 10.4%, respectively. In the 8 patients examined by the DI method to measure baseline rCBF twice, the mean and the SD of percentage differences between the two consecutive measurements in rCBF were -1.3% and 5.5%, respectively. Eight out of 14 patients with occlusive disease had at least one region with a CVR less than 10%. They showed a significant increase in resting rCBF after CR, not only in the ipsilateral hemisphere (from 26.1 +/- 6.4 to 33.4 +/- 4.7) but also in the contralateral one (from 28.3 +/- 7.0 to 34.7 +/- 4.7) with a recovery of the ipsilateral CVR from 9.3 +/- 17.2 to 41.2 +/- 20.1%. The remaining six patients with good-moderate CVR did not show an increase in rCBF after CR (from 28.0 +/- 2.7 to 28.3 +/- 3.4). The three of them with a moderate CVR (10-25%) before CR showed normalization of CVR after CR. CONCLUSION: Patients with decreased rCBF and reduced CVR benefited from CR in terms of an increase in rCBF and recovery of CVR. The quantitative double-injection IMP-SPECT has the ability to identify those patients who may benefit from CR.