In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18-Labeled THK5351.

Importance: In vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation. Objective: To investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)-binding fluorine 18 ([18F])-labeled THK5351 positron emission tomography (PET). Design, Setting, and Participants: In this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals. Main Outcomes and Measures: Standardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores. Results: A total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)-corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia. Conclusions and Relevance: This case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.

Endolymphatic hydrops asymmetry distinguishes patients with Meniere's disease from normal controls with high sensitivity and specificity.

Background: Many endolymphatic hydrops (EH) MRI studies in the literature do not include a normal control group. Consequently, it remains unclear which outcome measure in EH MRI can most effectively distinguish between MD patients and normal controls. Methods: Gadolinium-enhanced EH imaging was performed to quantitatively evaluate the extents of hydrops in MD patients and age-/sex-matched normal controls. Four hours after intravenous injection of contrast agent, MRI was performed using a 3-T MR platform fitted with a 32-channel phased-array coil receptor. MR images (10-15 slices) covering an inner ear were 3D-stacked. Analyses of all images that included the vestibule or the cochlea yielded the volumes (in µL) of the endolymphatic and perilymphatic spaces. Results: For the vestibule, they were significantly greater EH% in ipsilateral (52.4 ± 12.5) than in contralateral MD ears (40.4 ± 8.5, p = 0.001) and in ipsilateral MD ears than in control ears (42.4 ± 13.7, p = 0.025). For the cochlea, the values were slightly higher EH% in ipsilateral MD ears (49.7 ± 10.4, p = 0.061) but did not significantly differ from contralateral (41.3 ± 12.6) or control ears (39.6 ± 18.9, p = 0.858). In the MD group, the EH asymmetries were 12.0 ± 10.2% (vestibule) and 8.4 ± 8.6% (cochlea), significantly larger than those of controls. Conclusion: Compared to conventional semiquantitative grading or quantitative EH% analysis, EH asymmetry may better distinguish MD patients from normal controls. Quantitative hydrops volumetric analysis yields clinically relevant information on inner ear function.

Three-Dimensional Volumetric Measurement of Endolymphatic Hydrops in Meniere's Disease.

Objective: We used volumetric three-dimensional (3D) analysis to quantitatively evaluate the extent of endolymphatic hydrops (EH) in the entire inner ear. We tested for correlations between the planimetric and volumetric measurements, to identify their advantages and disadvantages. Methods: HYDROPS2-Mi2 EH images were acquired for 32 ears (16 patients): 16 ipsilateral ears of MD patients (MD-ears) and 16 contralateral ears. Three-T MR unit with a 32-channel phased-array coil/the contrast agent to fill the perilymphatic space and the HYDROPS2-Mi2 sequence. We calculated the EH% [(endolymph)/(endolymph+perilymph)] ratio and analyzed the entire inner ear in terms of the volumetric EH% value, but only single cochlear and vestibular slices were subjected to planimetric EH% evaluation. The EH% values were compared between MD ears and non-MD ears, to evaluate the diagnostic accuracy of the two methods. Results: The volumetric EH% was significantly higher for MD vestibules (50.76 ± 13.78%) than non-MD vestibules (39.50 ± 8.99%). The planimetric EH% was also significantly higher for MD vestibules (61.98 ± 20.65%) than non-MD vestibules (37.22 ± 12.95%). The vestibular and cochlear volumetric EH% values correlated significantly with the planimetric EH% values of the MD ear. Conclusion: Volumetric and planimetric EH measurements facilitate diagnosis of MD ears compared to non-MD ears. Both methods seem to be reliable and consistent; the measurements were significantly correlated in this study. However, the planimetric EH% overestimates the extent of vestibular hydrops by 26.26%. Also, planimetric data may not correlate with volumetric data for non-MD cochleae with normal EH% values.

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging.

UNLABELLED: Visualization of biologic processes at molecular and cellular levels has revolutionized the understanding and treatment of human diseases. However, no single biomedical imaging modality provides complete information, resulting in the emergence of multimodal approaches. Combining state-of-the-art PET and MRI technologies without loss of system performance and overall image quality can provide opportunities for new scientific and clinical innovations. Here, we present a multiparametric PET/MR imager based on a small-animal dedicated, high-performance, silicon photomultiplier (SiPM) PET system and a 7-T MR scanner. METHODS: A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm(3) (filtered backprojection/ordered-subset expectation maximization) was developed. The SiPM PET insert was placed between the mouse body transceiver coil and gradient coil of a 7-T small-animal MRI scanner for simultaneous PET/MRI. Mutual interference between the MRI and SiPM PET systems was evaluated using various MR pulse sequences. A cylindric corn oil phantom was scanned to assess the effects of the SiPM PET on the MR image acquisition. To assess the influence of MRI on the PET imaging functions, several PET performance indicators including scintillation pulse shape, flood image quality, energy spectrum, counting rate, and phantom image quality were evaluated with and without the application of MR pulse sequences. Simultaneous mouse PET/MRI studies were also performed to demonstrate the potential and usefulness of the multiparametric PET/MRI in preclinical applications. RESULTS: Excellent performance and stability of the PET system were demonstrated, and the PET/MRI combination did not result in significant image quality degradation of either modality. Finally, simultaneous PET/MRI studies in mice demonstrated the feasibility of the developed system for evaluating the biochemical and cellular changes in a brain tumor model and facilitating the development of new multimodal imaging probes. CONCLUSION: We developed a multiparametric imager with high physical performance and good system stability and demonstrated its feasibility for small-animal experiments, suggesting its usefulness for investigating in vivo molecular interactions of metabolites, and cross-validation studies of both PET and MRI.

Early prediction of response to neoadjuvant chemotherapy in breast cancer patients: comparison of single-voxel (1)H-magnetic resonance spectroscopy and (18)F-fluorodeoxyglucose positron emission tomography.

OBJECTIVES: To prospectively compare performances of single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pathologic response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Thirty-five breast cancer patients who received NAC and subsequent surgery were prospectively enrolled. MRS and FDG-PET were performed before and after the 1st NAC cycle. Percentage changes of total choline-containing compounds (tCho) via MRS, and maximum and peak standardized uptake values (SUVmax, SUVpeak) and total lesion glycolysis (TLG) via FDG-PET were measured, and their performances in predicting pathologic complete response (pCR) were compared. RESULTS: Of the 35 patients, 6 showed pCR and 29 showed non-pCR. Mean % reductions of tCho, SUVmax, SUVpeak, and TLG of the pCR group were larger than those of the non-pCR group (-80.3 ± 13.9 % vs. -32.1 ± 49.4 %, P = 0.025; -54.7 ± 22.1 % vs. -26.3 ± 33.7 %, P = 0.058; -60.7 ± 18.3 % vs. -32.3 ± 23.3 %, P = 0.009; -89.5 ± 8.5 % vs. -52.6 ± 36.2 %, P = 0.020). Diagnostic accuracy (area under ROC curve; Az, 0.911) of the % reduction of tCho was comparable to those of %SUVmax (0.822), SUVpeak (0.862), and TLG (0.879) in distinguishing pCR from non-pCR (all P > 0.05). CONCLUSION: MRS showed comparable performance to FDG-PET in early prediction of pCR in breast cancer patients. KEY POINTS: • MRS can predict response to NAC in breast cancer post-1 (st) cycle. • Changes in tCho and SUV after NAC reflect tumour cellularity changes. • MRS can be an alternative to FDG-PET in predicting response to NAC.

MRI-Based Attenuation Correction for PET/MRI Using Multiphase Level-Set Method.

UNLABELLED: Inaccuracy in MR image-based attenuation correction (MR-AC) leads to errors in quantification and the misinterpretation of lesions in brain PET/MRI studies. To resolve this problem, we proposed an improved ultrashort echo time MR-AC method that was based on a multiphase level-set algorithm with main magnetic field (B0) inhomogeneity correction. We also assessed the feasibility of this level-set-based MR-AC method (MR-AC(level)), compared with CT-AC and MR-AC provided by the manufacturer of the PET/MRI scanner (MR-AC(mMR)). METHODS: Ten healthy volunteers and 20 Parkinson disease patients underwent(18)F-FDG and(18)F-fluorinated-N-3-fluoropropyl-2-ß-carboxymethoxy-3-ß-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET scans, respectively, using both PET/MRI and PET/CT scanners. The level-set-based segmentation algorithm automatically delimited air, bone, and soft tissue from the ultrashort echo time MR images. For the comparison, MR-AC maps were coregistered to reference CT. PET sinogram data obtained from PET/CT studies were then reconstructed using the CT-AC, MR-AC(mMR), and MR-AC(level) maps. The accuracies of SUV, SUVr (SUV and its ratio to the cerebellum), and specific-to-nonspecific binding ratios obtained using MR-AC(level) and MR-AC(mMR) were compared with CT-AC using region-of-interest- and voxel-based analyses. RESULTS: There was remarkable improvement in the segmentation of air cavities and bones and the quantitative accuracy of PET measurement using the level set. Although the striatal and cerebellar activities in (18)F-FP-CIT PET and frontal activity in (18)F-FDG PET were significantly underestimated by the MR-AC(mMR), the MR-AC(level) provided PET images almost equivalent to the CT-AC images. PET quantification error was reduced by a factor of 3 using MR-AC(level) (SUV error < 10% in MR-AC(level) and < 30% in MR-AC(mMR) [version VB18P], and < 5% in MR-AC(level) and < 15% in MR-AC(mMR) [VB20P]). CONCLUSION: The results of this study indicate that our new multiphase level-set-based MR-AC method improves the quantitative accuracy of brain PET in PET/MRI studies.

Whole-brain diffusion-tensor changes in parkinsonian patients with impulse control disorders.

BACKGROUND AND PURPOSE: The aim of this study was to determine the changes in diffusion-tensor images associated with medication-related impulse control disorder (ICD) in Parkinson's disease (PD) patients undergoing chronic dopamine-replacement therapy. METHODS: Nineteen PD patients, comprising 10 with ICD (PD-ICD) and 9 without ICD (PD-nonICD), and 18 age-matched healthy controls (HCs) with no cognitive or other psychiatric disorders were analyzed. All subjects underwent 3-T magnetic resonance diffusion-tensor imaging. For all PD patients, clinical data on PD duration, antiparkinsonian medication dosages, Unified Parkinson's Disease Rating Scale and Mini-Mental State Examination were collected. Whole-brain voxel-based measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed. RESULTS: In comparison with HCs, the PD-nonICD subjects had low FA at the bilateral orbitofrontal areas. While the PD-ICD subjects exhibited no such difference, their FA was significantly elevated at the anterior corpus callosum. Analysis of FA between the two PD groups revealed that FA in the anterior corpus callosum, right internal capsule posterior limbs, right posterior cingulum, and right thalamic radiations were significantly higher (corrected p<0.05) in the PD-ICD than in the PD-nonICD patients. MD did not differ between the PD-ICD and PD-nonICD groups in any brain regions. CONCLUSIONS: The PD-ICD patients appear to have relatively preserved white-matter integrity in the regions involved in reward-related behaviors compared to PD-nonICD patients. Further investigation is required to determine whether the difference in FA between PD-ICD and PD-nonICD patients reflects microstructural differences in the pathological progression of PD or is secondary to ICD.

Functional dysconnectivity of corticostriatal circuitry and differential response to methylphenidate in youth with attention-deficit/hyperactivity disorder.

BACKGROUND: Brain frontostriatal circuits have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, effects of methylphenidate on circuit-level functional connectivity are as yet unclear. The aim of the present study was to comprehensively investigate the functional connectivity of major striatal subregions in children with ADHD, including subanalyses directed at mapping cognitive and treatment response characteristics. METHODS: Using a comprehensive seeding strategy, we examined resting-state functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen in children and adolescents with ADHD and in age- and sex-matched healthy controls. RESULTS: We enrolled 83 patients with ADHD and 22 controls in our study. Patients showed significantly reduced dorsal caudate functional connectivity with the superior and middle prefrontal cortices as well as reduced dorsal putamen connectivity with the parahippocampal cortex. These connectivity measures were correlated in opposite directions in patients and controls with attentional performance, as assessed using the Continuous Performance Test. Patients showing a good response to methylphenidate had significantly reduced ventral caudate/nucleus accumbens connectivity with the inferior frontal cortices compared with poor responders. LIMITATIONS: Possible confounding effects of age-related functional connectivity change were not excluded owing to the wide age range of participants. CONCLUSION: We observed a region-specific effect of methylphenidate on resting-state functional connectivity, suggesting the pretreatment level of ventral frontostriatal functional connectivity as a possible methylphenidate response biomarker of ADHD.

COMT genotype affects brain white matter pathways in attention-deficit/hyperactivity disorder.

Increased dopamine availability may be associated with impaired structural maturation of brain white matter connectivity. This study aimed to derive a comprehensive, whole-brain characterization of large-scale axonal connectivity differences in attention-deficit/hyperactivity disorder (ADHD) associated with catechol-O-methyltransferase gene (COMT) Val158Met polymorphism. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in youth with ADHD who were COMT Val-homozygous (N = 29) compared with those who were Met-carriers (N = 29). Additionally, we examined whether dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) polymorphisms were associated with white matter differences. Level of attention was assessed using the continuous performance test before and after an 8-week open-label trial of methylphenidate (MPH). A network of white matter connections linking 18 different brain regions was significantly weakened in youth with ADHD who were COMT Met-carriers compared to those who were Val-homozygous (P < 0.05, family-wise error-corrected). A measure of white matter integrity, fractional anisotropy, was correlated with impaired pretreatment performance in continuous performance test omission errors and response time variability, as well as with improvement in continuous performance test response time variability after MPH treatment. Altered white matter connectivity was exclusively based on COMT genotypes, and was not evident in DAT1 or DRD4. We demonstrated that white matter connectivity in youth with ADHD is associated with COMT Val158Met genotypes. The present findings suggest that different layers of dopamine-related genes and interindividual variability in the genetic polymorphisms should be taken into account when investigating the human connectome.

Intratumoral heterogeneity of breast cancer xenograft models: texture analysis of diffusion-weighted MR imaging.

OBJECTIVE: To investigate whether there is a relationship between texture analysis parameters of apparent diffusion coefficient (ADC) maps and histopathologic features of MCF-7 and MDA-MB-231 xenograft models. MATERIALS AND METHODS: MCF-7 estradiol (+), MCF-7 estradiol (-), and MDA-MB-231 xenograft models were made with approval of the animal care committee. Twelve tumors of MCF-7 estradiol (+), 9 tumors of MCF-7 estradiol (-), and 6 tumors in MDA-MB-231 were included. Diffusion-weighted MR images were obtained on a 9.4-T system. An analysis of the first and second order texture analysis of ADC maps was performed. The texture analysis parameters and histopathologic features were compared among these groups by the analysis of variance test. Correlations between texture parameters and histopathologic features were analyzed. We also evaluated the intraobserver agreement in assessing the texture parameters. RESULTS: MCF-7 estradiol (+) showed a higher standard deviation, maximum, skewness, and kurtosis of ADC values than MCF-7 estradiol (-) and MDA-MB-231 (p < 0.01 for all). The contrast of the MCF-7 groups was higher than that of the MDA-MB-231 (p = 0.004). The correlation (COR) of the texture analysis of MCF-7 groups was lower than that of MDA-MB-231 (p < 0.001). The histopathologic analysis showed that Ki-67mean and Ki-67diff of MCF-7 estradiol (+) were higher than that of MCF-7 estradiol (-) or MDA-MB-231 (p < 0.05). The microvessel density (MVD)mean and MVDdiff of MDA-MB-231 were higher than those of MCF-7 groups (p < 0.001). A diffuse-multifocal necrosis was more frequently found in MDA-MB-231 (p < 0.001). The proportion of necrosis moderately correlated with the contrast (r = -0.438, p = 0.022) and strongly with COR (r = 0.540, p = 0.004). Standard deviation (r = 0.622, r = 0.437), skewness (r = 0.404, r = 0.484), and kurtosis (r = 0.408, r = 0.452) correlated with Ki-67mean and Ki-67diff (p < 0.05 for all). COR moderately correlated with Ki-67diff (r = -0.388, p = 0.045). Skewness (r = -0.643, r = -0.464), kurtosis (r = -0.581, r = -0.389), contrast (r = -0.473, r = -0.549) and COR (r = 0.588, r = 0.580) correlated with MVDmean and MVDdiff (p < 0.05 for all). CONCLUSION: The texture analysis of ADC maps may help to determine the intratumoral spatial heterogeneity of necrosis patterns, amount of cellular proliferation and the vascularity in MCF-7 and MDA-MB-231 xenograft breast cancer models.

Diffusion tensor tractography analysis of the corpus callosum fibers in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Involvement of the corpus callosum (CC) is reported to be a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC pathology using diffusion tensor tractography analysis to identify precisely which fiber bundles are involved in ALS. METHODS: Diffusion tensor imaging was performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole brain tractography was performed using the multiple-region of interest (ROI) approach, and CC fiber bundles were extracted in two ways based on functional and structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs), and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer software, respectively. RESULTS: The mean fractional anisotropy (FA) values of the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6), and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS patients than in controls, whereas those of the primary sensory cortex (BA1, BA2, BA3), Broca's area (BA44/45), and the orbitofrontal cortex (BA11/47) did not differ significantly between the two groups. The FreeSurfer ROI approach revealed a very similar pattern of abnormalities. In addition, a significant correlation was found between the mean FA value of the CC fibers interconnecting the primary motor area and disease severity, as assessed using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor neuron signs. CONCLUSIONS: Our findings suggest that there is some degree of selectivity or a gradient in the CC pathology in ALS. The CC fibers interconnecting the primary motor and dorsolateral prefrontal cortices may be preferentially involved in ALS.

Connectomic disturbances in attention-deficit/hyperactivity disorder: a whole-brain tractography analysis.

BACKGROUND: Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD. METHODS: Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in 71 children and adolescents with ADHD compared with 26 healthy control subjects. White matter differences were further delineated between patients with (n = 40) and without (n = 26) the predominantly hyperactive/impulsive subtype of ADHD. RESULTS: A significant network comprising 25 distinct fiber bundles linking 23 different brain regions spanning frontal, striatal, and cerebellar brain regions showed altered white matter structure in ADHD patients (p < .05, family-wise error-corrected). Moreover, fractional anisotropy in some of these fiber bundles correlated with attentional disturbances. Attention-deficit/hyperactivity disorder subtypes were differentiated by a right-lateralized network (p < .05, family-wise error-corrected) predominantly linking frontal, cingulate, and supplementary motor areas. Fractional anisotropy in this network was also correlated with continuous performance test scores. CONCLUSIONS: Using an unbiased, whole-brain, data-driven approach, we demonstrated abnormal white matter connectivity in ADHD. The correlations observed with measures of attentional performance underscore the functional importance of these connectomic disturbances for the clinical phenotype of ADHD. A distributed pattern of white matter microstructural integrity separately involving frontal, striatal, and cerebellar brain regions, rather than direct frontostriatal connectivity, appears to be disrupted in children and adolescents with ADHD.

Extrastriatal dopaminergic changes in Parkinson's disease patients with impulse control disorders.

OBJECTIVE: To investigate the extrastriatal dopaminergic neural changes in relation to the medication-related impulse control disorders (ICD) in Parkinson's disease (PD). METHOD: A total of 31 subjects (11 and 11 drug-treated PD patients with and without medication-related ICDs and 9 healthy controls) having no other co-morbid psychiatric disorders participated in this study. Each subject underwent dynamic N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP) at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric maps of [(18)F]-FP-CIT binding were analysed by original and putaminal normalised manners. RESULTS: Compared with the healthy controls, BPs at both VMPFCs were significantly high and the extrastriatal to putaminal BP ratios at all regions were approximately three times higher in both PD groups. The PD ICD patients showed significantly higher BPs at the right VMPFC and tendency to lower BPs at the left nucleus accumbens compared with those free of ICD. The ICD subjects also showed reduced uptakes at both ventral striatal regions in the original parametric analysis and higher uptakes at the left insular and right posterior cingulate cortex and lower uptakes at both ventral pallidums in the putaminal normalised parametric analysis compared with the non-ICD subjects. CONCLUSIONS: A great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal changes between the ICD and non-ICD patients could provide a further insight into a mechanism of ICD in PD.

Effect of delayed transit time on arterial spin labeling: correlation with dynamic susceptibility contrast perfusion magnetic resonance in moyamoya disease.

OBJECTIVES: Because arterial spin labeling (ASL) is completely noninvasive and provides absolute cerebral blood flow (CBF) information within a brief period, the technique has been increasingly used for patients with acute or chronic cerebrovascular disease. However, the effect of delayed transit time on ASL can generate errors in the quantitative estimation of CBF using ASL. Furthermore, in the clinical setting, in which transit time is uncertain, the variability of the transit time in patients reduces the validity of CBF on ASL images. Therefore, we evaluated the effect of delayed transit time on ASL images compared with dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) in patients with moyamoya disease. MATERIALS AND METHODS: Arterial spin labeling and DSC perfusion MR images were acquired in 54 patients with moyamoya disease. Vascular territory and anatomical structure-based regions of interest (ROIs) were applied to the CBF and time-to-peak (TTP) maps from DSC and a CBF map using ASL. The change of the correlation coefficient (r) between normalized CBFs (nCBFs) from DSC and ASL was evaluated with categorization by the TTP. In addition, the dependence of the difference between the nCBF values from DSC and ASL on the TTP obtained using DSC was also analyzed. RESULTS: The nCBF values from DSC and ASL were strongly correlated (r = 0.877 and r = 0.867 for the internal carotid artery (ICA) and middle cerebral artery territory-based ROIs, respectively; P < 0.0002 for both; r = 0.783 for the anatomical structure-based ROIs; P < 0.0084). However, correlations between nCBFs from DSC and ASL tended to be weaker when the TTP increased, with recovery when the TTP was extremely delayed (>25 seconds). The TTP delay had a positive effect on the difference between the nCBF values from the DSC and ASL for the ICA territory-based and anatomical structure-based ROIs (standardized coefficients, 0.224 for the ICA territory-based ROIs; P = 0.0410; 0.189 for the anatomical structure-based ROIs; P < 0.0084). CONCLUSIONS: Our results demonstrate that the correlation between the CBF values from the ASL and DSC tends to be weaker when the transit time is more delayed, with the restoration of the strength of the correlation when the TTP is extremely delayed (>25 seconds). Understanding the effect of delayed transit time on the CBF from ASL perfusion MR in a clinical setting would facilitate the proper interpretation of ASL images.

Serial MR analysis of early permanent and transient ischemia in rats: diffusion tensor imaging and high b value diffusion weighted imaging.

OBJECTIVE: To evaluate the temporal evolution and diagnostic values of the diffusion tensor imaging (DTI) and the high b value diffusion weighted imaging (DWI) in the early permanent and transient cerebral ischemia. MATERIALS AND METHODS: For permanent or 30-minute transient-ischemia induced 30 rats, DTI and DWIs at both high b (b = 3000 s/mm(2)) and standard b value (b = 1000 s/mm(2)) were obtained at the following conditions: at 15, 30, 45, 60 minutes after the occlusion of what for hyperacute permanent ischemia; at 1, 3, 5, 7, 9 hours after the occlusion for acute permanent ischemia; and at 15 minutes before reperfusion, 0.5, 2.5, and 24 hours after reperfusion for transient ischemia. The diffusion parameters and their ratios were obtained and compared between different b values, and among different time points and groups, respectively. RESULTS: For both b values, the apparent diffusion coefficient (ADC) ratio decreased for first three hours, and then slightly increased until 9 hours after the occlusion during a gradual continuous increase of DWI signal intensity (SI) ratio, with excellent correlation between ADC ratios and DWI SI ratios. The DWI showed a higher contrast ratio, but the ADC map showed a lower contrast ratio for permanent ischemia at high b value than at standard b value. Fractional anisotropy (FA) increased for 1 hour, then gradually decreased until 9 hours after the occlusion in permanent ischemia and showed transient normalization and secondary decay along with change in ADC in transient ischemia. CONCLUSION: This study presents characteristic initial elevation and secondary decay of FA, higher contrast ratio of DWI, and lower contrast ratio of ADC map at high b value, in addition to the time evolutions of diffusion parameters in early permanent and transient ischemia.

Comparison of segmentation-based attenuation correction methods for PET/MRI: evaluation of bone and liver standardized uptake value with oncologic PET/CT data.

UNLABELLED: For attenuation correction (AC) in PET/MRI systems, segmentation-based methods are most often used. However, the standardized uptake value (SUV) of lesions in the bone and liver, which have higher attenuation coefficients than other organs, can be underestimated, potentially leading to misinterpretation of clinical cases. Errors in SUV estimation are also dependent on the segmentation schemes used in the segmentation-based AC. In this study, this potential bias in SUV estimation using 4 different segmentation-based AC methods was evaluated for the PET/CT data of cancer patients with bone and liver lesions. METHODS: Forty patients who had spine or liver lesions and underwent (18)F-FDG PET/CT participated (18 women and 22 men; 20 spine lesions and 20 liver lesions; mean age (± SD), 60.5 ± 11.4 y; mean body weight, 57.7 ± 10.4 kg). The patient body region was extracted from the CT image and categorized into 5 tissue groups (air, lungs, fat, water, and bone) using Hounsfield unit thresholds, which were determined from the CT histogram. Four segmentation-based AC methods (SLA [soft-tissue/lung/air], WFLA [water/fat/lung/air], SLAB [soft-tissue/lung/air/bone], and WFLAB [water/fat/lung/air/bone]) were compared with CT-based AC. The mean attenuation coefficient for each group was calculated from 40 CT images and assigned to the attenuation maps. PET sinograms were reconstructed using segmentation- and CT-based AC maps, and mean SUV in the lesions was compared. RESULTS: Mean attenuation coefficients for air, lungs, fat, water, and bone were 0.0058, 0.0349, 0.0895, 0.0987, and 0.1178 cm(-1), respectively. In the spine lesions, the SUVs were underestimated by 16.4% ± 8.5% (SLA AC) and 14.7% ± 7.5% (WFLA AC) but not to a statistically significant extent for SLAB and WFLAB AC relative to CT AC. In the liver lesions, the SUVs were underestimated by 11.1% ± 2.6%, 8.1% ± 3.0%, 6.8% ± 3.8%, and 4.1% ± 3.8% with SLA, SLAB, WFLA, and WFLAB AC, respectively. CONCLUSION: Without bone segmentation, the SUVs of spine lesions were considerably underestimated; however, the bias was acceptable with bone segmentation. In liver lesions, the segmentation-based AC methods yielded a negative bias in SUV; however, inclusion of the bone and fat segments reduced the SUV bias. The results of this study will be useful for understanding organ-dependent bias in SUV between PET/CT and PET/MRI.

Hydrotropic magnetic micelles for combined magnetic resonance imaging and cancer therapy.

Polymeric nanoparticles, capable of encapsulating imaging agents and therapeutic drugs, have significant advantages for simultaneous diagnosis and therapy. Nonetheless, improvements in the loading contents of the active agents are needed to achieve enhanced imaging and effective therapeutic outcomes. Aiming to make these improvements, a hydrotropic micelle (HM) was explored to encapsulate superparamagnetic iron oxide nanoparticles (SPIONs) as the magnetic resonance (MR) imaging agent and paclitaxel (PTX) as the hydrophobic anticancer drug. Owing to its hydrotropic inner core with hydrophobic nature, HM could effectively encapsulate both of PTX and SPION via the simple dialysis method. The hydrodynamic size of HM increased from 68 to 178nm after physical encapsulation of SPION and PTX. Transmission electron microscopy analysis of HM bearing SPION and PTX (HM-SPION-PTX) revealed a spherical morphology with SPION clusters in the micelle cores. The micelles released PTX in a sustained manner. The bare HM and HM-SPION showed no toxicity to SCC7 cells, whereas HM-PTX and HM-SPION-PTX showed dose-dependent cytotoxicity that was lower than free PTX. HM-SPION-PTX exhibited 8.1-fold higher T(2) relaxivity than HM-SPION, implying potential of HM-SPION-PTX as the contrast agent for MR imaging. When systemically administered to tumor-bearing mice, HM-SPION-PTX was effectively accumulated at the tumor site, allowing its detection using MR imaging and effective therapy. Overall, these results suggested that HM-SPION-PTX is a promising candidate for combined diagnosis and treatment of cancer.

SiPM-PET with a short optical fiber bundle for simultaneous PET-MR imaging.

For positron emission tomography (PET) inserts to magnetic resonance imaging (MRI) applications, optical fibers have been used for some time to transfer scintillation photons to photomultiplier tubes positioned outside the fringe magnetic field. We previously proposed a novel utilization of an optical fiber for good radio frequency (RF) transmission from body coils to an imaging object. Optical fiber bundles between silicon photomultipliers (SiPM) and scintillation crystals provide an increased spacing between RF-shielded electronics boxes, facilitating RF passage from the body RF coils to imaging objects. In this paper, we present test results of a SiPM-PET system with a short optical fiber bundle for simultaneous PET-MR imaging. We built the SiPM-PET system which consisted of 12 SiPM-PET modules; each module was assembled with a lutetium yttrium oxyorthosilicatecrystal block, a 31 mm optical fiber bundle, a Hamamatsu multi-pixel photon counter S11064-050P and a signal processing box shielded with copper. The SiPM-PET system, with a face-to-face distance of 71 mm, was placed inside a 3 T MRI. A small surface coil placed inside the SiPM-PET system was used to receive the signal from phantoms while the body RF coil transmitted the RF pulses. The SiPM-PET system showed little performance degradation during the simultaneous PET-MR imaging and it caused no significant degradation of MR images with turbo spin echo (TSE), gradient echo or 3D spoiled gradient recalled sequences. Echo planar imaging MR images with and without the SiPM-PET inside the MR scanner were significantly worse than the images obtained with the TSE sequence.