Assessing interstitial fluid dynamics in type 2 diabetes mellitus and prediabetes cases through diffusion tensor imaging analysis along the perivascular space.

Background and purpose: Glymphatic system in type 2 diabetes mellitus (T2DM) but not in the prodrome, prediabetes (Pre-DM) was investigated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Association between glymphatic system and insulin resistance of prominent characteristic in T2DM and Pre-DM between is yet elucidated. Therefore, this study delves into the interstitial fluid dynamics using the DTI-ALPS in both Pre-DM and T2DM and association with insulin resistance. Materials and methods: In our cross-sectional study, we assessed 70 elderly individuals from the Bunkyo Health Study, which included 22 with Pre-DM, 18 with T2DM, and 33 healthy controls with normal glucose metabolism (NGM). We utilized the general linear model (GLM) to evaluate the ALPS index based on DTI-ALPS across these groups, considering variables like sex, age, intracranial volume, years of education, anamnesis of hypertension and hyperlipidemia, and the total Fazekas scale. Furthermore, we have explored the relationship between the ALPS index and insulin resistance, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using GLM and the same set of covariates. Results: In the T2DM group, the ALPS index demonstrated a reduction compared with the NGM group [family-wise error (FWE)-corrected p < 0.001; Cohen's d = -1.32]. Similarly, the Pre-DM group had a lower ALPS index than the NGM group (FWE-corrected p < 0.001; Cohen's d = -1.04). However, there was no significant disparity between the T2DM and Pre-DM groups (FWE-corrected p = 1.00; Cohen's d = -0.63). A negative correlation was observed between the ALPS index and HOMA-IR in the combined T2DM and Pre-DM groups (partial correlation coefficient r = -0.35, p < 0.005). Conclusion: The ALPS index significantly decreased in both the pre-DM and T2DM groups and showed a correlated with insulin resistance. This indicated that changes in interstitial fluid dynamics are associated with insulin resistance.

Association between mammillary body atrophy and memory impairment in retired athletes with a history of repetitive mild traumatic brain injury.

Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV-adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK-SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann-Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10-3, p < 0.001). The MBs volume/TBV ratio correlated with visual memory, as assessed, respectively, by the Rey-Osterrieth Complex Figure test delayed recall (ρ = 0.62, p < 0.001). In conclusion, retired athletes with rmTBI have MB atrophy, potentially contributing to memory impairment linked to the Papez circuit disconnection.

[Challenges of Diagnostic Imaging of Chronic Traumatic Encephalopathy].

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury (rmTBI). Clinically, CTE experienced by athletes with rmTBI can lead to long-term neurological impairment, including memory disturbances, Parkinsonism, behavioral changes, speech irregularities, and gait abnormalities, formerly described as punch-drunk syndrome and dementia pugilistica. CTE has gained significant public interest owing to dramatic cases involving retired professional athletes wherein severe behavioral problems and tragic incidents were reported. However, no reliable biomarkers of late-onset neurodegenerative diseases following TBI are available, and a definitive diagnosis can only be made via postmortem neuropathological examination. CTE is characterized by abnormal accumulation of hyperphosphorylated tau proteins. Neuropathological studies have revealed that CTE demonstrates a unique pattern of tau pathology in neurons and astrocytes and accumulation of other misfolded proteins such as TDP-43. Furthermore, gross pathological findings were revealed, especially in severe CTE. Thus, we hypothesized that objective neuroimaging patterns linking the history of rmTBI or CTE might be established using tau positron emission tomography (PET) and magnetic resonance imaging (MRI). In this review, we present the clinical and neuropathological features of CTE and our efforts to develop a prenatal diagnostic method using MRI and tau PET. The unique findings of tau PET images and various signal and morphological abnormalities on conventional MRI in retired athletes with rmTBI may be useful in diagnosing CTE.

Glymphatic system impairment in nonathlete older male adults who played contact sports in their youth associated with cognitive decline: A diffusion tensor image analysis along the perivascular space study.

Background and purpose: Exposure to contact sports in youth causes brain health problems later in life. For instance, the repetitive head impacts in contact sports might contribute to glymphatic clearance impairment and cognitive decline. This study aimed to assess the effect of contact sports participation in youth on glymphatic function in old age and the relationship between glymphatic function and cognitive status using the analysis along the perivascular space (ALPS) index. Materials and methods: A total of 52 Japanese older male subjects were included in the study, including 12 who played heavy-contact sports (mean age, 71.2 years), 15 who played semicontact sports (mean age, 73.1 years), and 25 who played noncontact sports (mean age, 71.3 years) in their youth. All brain diffusion-weighted images (DWIs) of the subjects were acquired using a 3T MRI scanner. The ALPS indices were calculated using a validated semiautomated pipeline. The ALPS indices from the left and right hemispheres were compared between groups using a general linear model, including age and years of education. Furthermore, partial Spearman's rank correlation tests were performed to assess the correlation between the ALPS indices and cognitive scores (Mini-Mental State Examination and the Japanese version of the Montreal Cognitive Assessment [MoCA-J]) after adjusting for age years of education and HbA1c. Results: The left ALPS index was significantly lower in the heavy-contact and semicontact groups than that in the noncontact group. Although no significant differences were observed in the left ALPS index between the heavy-contact and semicontact groups and in the right ALPS index among groups, a trend toward lower was found in the right ALPS index in individuals with semicontact and heavy-contact compared to the noncontact group. Both sides' ALPS indices were significantly positively correlated with the MoCA-J scores. Conclusion: The findings indicated the potential adverse effect of contact sports experience in youth on the glymphatic system function in old age associated with cognitive decline.

Superior cerebellar peduncle atrophy of progressive supranuclear palsy on phase difference enhanced imaging: a comparison with Parkinson's disease.

PURPOSE: Phase difference enhanced (PADRE) imaging can enhance myelin density and delineate the superior cerebellar peduncle (SCP). We aimed to determine if SCP atrophy was distinguishable on PADRE imaging and evaluate its diagnostic performance compared with previous MRI progressive supranuclear palsy (PSP) findings. METHODS: Two reviewers measured the SCP widths on PADRE in 20 PSP and 31 Parkinson's disease (PD) patients. The SCP and middle cerebellar peduncle (MCP) widths and the pons and midbrain areas were measured on 3D-T1WI, and the ratio of the area of the pons to the area of the midbrain, the MCP/SCP ratio, and the magnetic resonance parkinsonism index (MRPI) were calculated. We used the Steel-Dwass test to compare PSP, PD, and HS, and receiver operating characteristic curve (ROC) analyses to assess the sensitivity and specificity for diagnosing PSP from PD. A comparison of ROC curves was performed between the SCP on PADRE and these 3D-T1WI parameters. RESULTS: In radiologist 1, the SCP on PADRE in PSP (1.1 ± 0.3 mm) was significantly smaller than those in PD (2.4 ± 0.4 mm) (P < 0.001); the area under the curve (AUC) was 0.97. At a 1.75-mm cutoff value, the diagnostic sensitivity and specificity for differentiating PSP from PD were 93.5% and 100%, respectively. The AUC of the SCP on PADRE was significantly higher than the 3D-T1WI parameters (the SCP, MCP, pons area, MCP/SCP ratio, and MRPI). CONCLUSION: Assessing SCP with PADRE imaging may yield high diagnostic accuracy for discriminating PSP from PD.

Optic radiation atrophy in Lewy body disease with visual hallucination on phase difference enhanced magnetic resonance images.

Visual hallucinations (VH) occur commonly in Lewy body disease (LBD), including Parkinson's disease (PD), PD with dementia, and dementia with Lewy bodies. We aimed to use phase difference enhanced imaging (PADRE) to assess structural abnormalities of optic radiation (OR) in patients with Lewy body disease (LBD) concomitant with VH. Firstly, two radiologists reviewed the OR appearances in healthy subjects (HS) on PADRE. Next, based on the OR abnormalities, two reviewers assessed the PADRE images from 18 HS and 38 and 110 patients with LBD, with and without VH, respectively, in a blinded manner. Finally, all patients with LBD without VH were eventually followed up for at least 5 years after magnetic resonance imaging to determine the appearance of VH. The radiologists identified three layers, namely external sagittal stratum, internal sagittal stratum, and tapetum, in OR on the PADRE in HS. Moreover, they were able to consensually define the OR as abnormal when the layers were obscured and the disappearance of the cranial side. The sensitivity/specificity of abnormal OR for each case was 68%/81% (LBD with VH vs. LBD without VH). Furthermore, VH appeared in 12 of the 21 (57%) patients with LBD and abnormal OR during the follow-up period. However, no patients without abnormal OR reported VH. Patients with LBD and VH demonstrated the abnormal OR. This, in turn, might be a useful marker to distinguish the patients with VH from those without VH and HS. Moreover, abnormal OR on PADRE may precede the appearance of VH in LBD.

Investigation into self-assembled collagen arrays guided by the surface properties of polyimide films.

The mechanism of highly-oriented collagen (Col) fibril arrays on rubbed polyimide (PI) films was investigated in order to understand the interfacial Col-PI interactions. It was found that the orientation of the surface functional groups of the rubbed PI films was most effectively controlled and optimized by the rubbing conditions. In particular, nano-grooves with a width of 100-600 nm and a depth of 2-10 nm were formed on the rubbed PI films at a rubbing strength of 2.4 m, leading to the formation of the highest density of the Col fibril array. Moreover, highly-oriented Col fibrils were formed inside the nano-grooves by the formation of hydrogen bonds between the CO of the imide groups (@ rubbed PI films) and the N-H of the amino groups (@ ß-Sheets of Col molecules), resulting in the orientation of the Col molecules and subsequent assembly to the fibrils. Thus, the orientation and density of the fibril arrays on the rubbed PI films were successfully controlled by the interfacial interactions between the ß-Sheet component of Col and the nano-groove surfaces of the rubbed PI films. Therefore, the novel technology of this study will provide an effective method to fabricate the one-directional fibrous nanostructures and to understand how to control the orientation of biomolecules in vitro.

Quantitative Susceptibility Mapping: Basic Methods and Clinical Applications.

Quantitative susceptibility mapping (QSM), one of the advanced MRI techniques for evaluating magnetic susceptibility, offers precise quantitative measurements of spatial distributions of magnetic susceptibility. Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and is a substance-specific value. Recently, QSM has been widely used to estimate various levels of substances in the brain, including iron, hemosiderin, and deoxyhemoglobin (paramagnetism), as well as calcification (diamagnetism). By visualizing iron distribution in the brain, it is possible to identify anatomic structures that are not evident on conventional images and to evaluate various neurodegenerative diseases. It has been challenging to apply QSM in areas outside the brain because of motion artifacts from respiration and heartbeats, as well as the presence of fat, which has a different frequency to the proton. In this review, the authors provide a brief overview of the theoretical background and analyze methods of converting MRI phase images to QSM. Moreover, we provide an overview of the current clinical applications of QSM. Online supplemental material is available for this article. ©RSNA, 2022.

Signal intensity of cerebral gyri in corticobasal syndrome on phase difference enhanced magnetic resonance images: Comparison of progressive supranuclear palsy and Parkinson's disease.

We evaluated cerebral gyri (CG) on phase difference enhanced imaging (PADRE) of corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Parkinson's disease (PD) patients to determine whether it is possible to discriminate among them on an individual basis. Two radiologists reviewed appearance of the normal CG and that of CBS patients on PADRE, and deviations from the appearance of the normal CG were recorded. Next, based on the CG abnormalities, two other reviewers reviewed PADRE images from 12 CBS, 14 PSP, and 30 PD patients. In healthy subjects on the PADRE images, the signal intensity (SI) of the gray matter (GM) was homogeneously, slightly hyperintense to the subcortical white matter (SCWM), and the SI of the SCWM was homogeneously hypointense. In CBS patients, hypointense layer in superficial GM and disappearance of hypointense in SCWM. The frequency of the abnormal findings on PADRE in the blinded manner by two readers was 100% (12/12), 3% (1/30), and 29% (4/14 in Reader 1) or 36% (5/14 in Reader 2) in CBS PD, and PSP patients, respectively. Laterality of the PADRE findings was showed in 12 (100%) CBS patients and 3 (21%) PSP, but not in any PD patients. The previously reported typical findings in CBS on conventional magnetic resonance image (MRIs) were observed in only 42% (5/12) of CBS patients. In conclusion, the abnormal findings in CG on PADRE appears more useful than conventional MRI findings for discriminating CBS from PD on an individual basis.

Facial nerve atrophy in patients with amyotrophic lateral sclerosis: Evaluation with fast imaging employing steady-state acquisition (FIESTA).

BACKGROUND: In amyotrophic lateral sclerosis (ALS), motor neurons in the brainstem markedly deplete, whereas sensory neurons are less severely affected. PURPOSE: To determine whether facial nerve (FN) measurement on 3D fast imaging employing steady-state acquisition (FIESTA) is useful for ALS diagnosis. STUDY TYPE: Retrospective. SUBJECTS: Fifteen ALS patients and 16 controls. FIELD STRENGTH/SEQUENCE: 3T FIESTA MR. ASSESSMENT: The cross-sectional area of the FN and cochlear nerve (CN) were measured, and the FN/CN ratio (FCR) was assessed. For qualitative assessment, the FN cross-sectional area was compared with that of the CN and the following scores were assigned: score 1 (large), the FN is larger than the CN; score 2 (almost equal), the size difference between the FN and CN is within 10%; score 3 (small), the FN is smaller than the CN (10-50%); score 4 (significantly small), size of the FN is less than half the size of the CN. STATISTICAL TESTS: The differences in FCR between the ALS patients and the controls were tested using the Wilcoxon Mann-Whitney U-test. For the qualitative and quantitative assessments, we performed a receiver operating characteristic analysis for the diagnosis of ALS with an abnormal finding as score 3 or 4. RESULTS: The mean FCR was significantly smaller for ALS patients (0.71 ± 0.17) than for controls (0.95 ± 0.08) (P < 0.001) and the area under the curve was 0.93. When an FN score was 3 or 4, indicative of FN atrophy, the sensitivity and specificity values of FIESTA for discriminating ALS patients from controls were 93.3% (14/15) and 90.0% (18/20), respectively. DATA CONCLUSION: The FN atrophy revealed on FIESTA, which may reflect lower motor neuron impairment in ALS, allowed us to distinguish ALS patients from controls with a high degree of accuracy. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:757-766.

Potential usefulness of signal intensity of cerebral gyri on quantitative susceptibility mapping for discriminating corticobasal degeneration from progressive supranuclear palsy and Parkinson's disease.

PURPOSE: The typical MRI findings in corticobasal degeneration (CBD), which have been described in previous reports, may be non-specific. We evaluated cerebral gyri (CG) using quantitative susceptibility mapping (QSM) images of patients with CBD, progressive supranuclear palsy (PSP), and Parkinson's disease (PD) to determine the possibility of discriminating them on an individual basis. METHODS: After reviewing the normal appearances on QSM on 16 healthy subjects, two radiologists assessed abnormal findings from 12 CBD, 14 PSP, and 30 PD patients. For conventional MRI, two radiologists independently reviewed typical CBD findings that have been previously reported. We also investigated three autopsy cases including one each of CBD, PSP, and PD to reveal the histopathological basis of MRI findings. RESULTS: CBD-specific findings included three layers; a higher susceptibility layer in superficial GM, a lower susceptibility layer, and a higher susceptibility layer in corticomedullary junction, with frequencies of 83% (10/12) in CBD, 21% (3/14) in PSP, and 0% (0/30) in PD patients. The typical CBD findings on conventional MRI were observed in only 42% (5/12) of CBD patients. Ferritin-positive microglia accumulated in the superficial gray matter (third cortical layer) and corticomedullary junction in CBD patients. CONCLUSIONS: The CG findings on QSM images may be more useful than those on conventional MRI for discriminating CBD from PD on an individual basis. Based on postmortem pathological data, cortical QSM hyperintensity might be an expression of ferritin-positive microglia.

Evaluation of oxygen extraction fraction in systemic lupus erythematosus patients using quantitative susceptibility mapping.

The purposes of this study are to assess the oxygen extraction fraction (OEF) changes on MRI-based quantitative susceptibility mapping (QSM) in systemic lupus erythematosus (SLE) patients and to determine whether QSM-OEF is associated with disease activity in SLE. We enrolled 42 SLE patients and 20 healthy subjects (HS) who had no pathologies on conventional brain MRI. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). For the measurement of QSM-OEF, QSM data were analysed using the Perfusion Mismatch Analyzer software program. Spearman's or Pearson's correlation coefficients were calculated, and independent predictors were identified through a multiple linear regression analysis. QSM-OEF was significantly higher in SLE than that in HS (51.3 ± 10.1 vs. 40.5 ± 3.7, p < 0.001). QSM-OEF was positively correlated with SLEDAI and the presence of neuropsychiatric symptom (NPS) scores (ρ = 0.663, p < 0.001 and ρ = 0.340, p = 0.028). At multiple linear regression analysis, SLEDAI and NPS were independently associated with QSM-OEF (standardized ß = 0.426, p = 0.016 and standardized ß = 6.148, p = 0.029). In the SLE patients, QSM-OEF is associated with disease activity, which might predict an increased risk of stroke in SLE.

[I Am Seeing a Human!: The Perception of an External Visual Stimulus Where None Exists].

A visual hallucination (VH) is "the perception of an external visual stimulus where none exists". It frequently occurs in Lewy body disease (LBD): Parkinson's disease and dementia with Lewy bodies. Although the exact pathogenesis of VH in patients with LBD is not clearly understood, many neuroimaging studies (structure MRI: brain volume, functional MRI, positron emission tomography, and single photon emission computerized tomography) have reported reduced gray matter volume, altered activation, and reduced metabolism in the dorsal and ventral visual pathways. The results obtained from the neuroimaging studies suggest the presence of aberrant visual information processing.

Hydrophobic Amino Acid Tryptophan Shows Promise as a Potential Absorption Enhancer for Oral Delivery of Biopharmaceuticals.

Cell-penetrating peptides (CPPs) have great potential to efficiently deliver drug cargos across cell membranes without cytotoxicity. Cationic arginine and hydrophobic tryptophan have been reported to be key component amino acids for cellular internalization of CPPs. We recently found that l-arginine could increase the oral delivery of insulin in its single amino acid form. Therefore, in the present study, we evaluated the ability of another key amino acid, tryptophan, to enhance the intestinal absorption of biopharmaceuticals. We demonstrated that co-administration with l-tryptophan significantly facilitated the oral and intestinal absorption of the peptide drug insulin administered to rats. Furthermore, l-tryptophan exhibited the ability to greatly enhance the intestinal absorption of other peptide drugs such as glucagon-like peptide-1 (GLP-1), its analog Exendin-4 and macromolecular hydrophilic dextrans with molecular weights ranging from 4000 to 70,000 g/mol. However, no intermolecular interaction between insulin and l-tryptophan was observed and no toxic alterations to epithelial cellular integrity-such as changes to cell membranes, cell viability, or paracellular tight junctions-were found. This suggests that yet to be discovered inherent biological mechanisms are involved in the stimulation of insulin absorption by co-administration with l-tryptophan. These results are the first to demonstrate the significant potential of using the single amino acid l-tryptophan as an effective and versatile bioavailability enhancer for the oral delivery of biopharmaceuticals.

Intracranial vessel wall lesions in patients with systematic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is related to vasculitis, which causes brain infarctions; however, the pathology of large cerebral vessels has not been fully established. PURPOSE: To demonstrate the prevalence of vessel wall lesions (VWLs) in SLE patients using 3D vessel wall imaging and to assess the relationship between VWLs and brain infarctions. STUDY TYPE: Retrospective. SUBJECTS: Sixty SLE patients and 50 healthy subjects (HS). FIELD STRENGTH/SEQUENCE: Each subject underwent 3T MRI, which included 3D FSE PDWI (CUBE). ASSESSMENT: For each of the 33 segments of the intracranial artery (internal carotid artery ∼ M3 segment of middle cerebral artery [MCA]), the VWLs were scored as either positive or negative, and the VWL score was calculated as the sum of the segments with VWLs. We also evaluated brain lesions on conventional MRI. STATISTICAL TESTS: We used logistic regression analyses to determine the clinical (serological test and cardiovascular risk factors) and imaging characteristics associated with infarctions in SLE patients. RESULTS: For the peripheral vessels such as MCA, VWLs were more common for SLE patients than for HS (43.3% versus 16.7% in M1 segment, 60.4% versus 16.7% in M2 segment, both P < 0.01). There were 21 infarctions in 13 patients (21.7%), and the median VWL score was larger in the patients with infarctions than in those without (13 versus 6, P < 0.01). Multivariate logistic regression analyses revealed a high VWL score ( ≥ 9) to be the only factor independently associated with the presence of infarctions (odds ratio: 10.1, 95% confidence interval: 1.01-101; P < 0.049). DATA CONCLUSION: We demonstrated a substantially high prevalence of VWLs among SLE patients, which were associated with brain infarctions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1237-1246.

Clinical performance metrics of 3D stereoscopic digital mammography compared with 2D digital mammography: observer study.

OBJECTIVE: To assess the clinical performance of three-dimensional stereoscopic digital mammography (3DsDM) compared with two-dimensional digital mammography (2DDM) for breast lesion diagnosis with jackknife free-response receiver operating characteristics (JAFROC) observer study. METHODS: 40 pairs of standard-dose 2DDM and their 3DsDM images were used for an observer performance study. A total of 18 lesions were identified as the reference standard of actionable breast lesions (Breast Imaging Reporting and Data System Category 3 or more) by two breast radiologists. Ratings and locations of "lesions" determined by observers were utilized for assessing the statistical significance of differences between eight radiologists' performances with the 2DDM images and with the 3DsDM images in jackknife free-response receiver operating characteristic analysis. RESULTS: The average figure-of-merit values for all radiologists increased to a statistically significant degree, from 0.859 with the 2DDM images to 0.936 with the 3DsDM images (p < 0.001). The average sensitivity for detecting actionable lesions was improved from 74.3 to 92.4% at a false-positive rate of 0.2 per case by use of the 3DsDM images. The mean reading time per case with 2DDM images was not significantly different from that with 3DsDM images. CONCLUSION: The use of 3DsDM would improve the observer performance for breast lesion without considerably extending the reading time. Advances in knowledge: Use of 3DsDM improves radiologists' performance for breast lesion detection.

Salvage radiotherapy for second oligo-recurrence in patients with breast cancer.

A new concept designated 'oligo-recurrence (OR)' has been proposed, which indicates one to several distant metastases/recurrences in one or more organs, which can be treated with local therapy, after the primary site of the cancer has been controlled. The purpose of this study was to assess the efficacy and toxicity of salvage radiotherapy (RT) for the second OR of breast cancer. The second OR was defined as once-salvaged patients with OR who had a second failure that was also detected as the state of OR. Twenty-one patients with second OR were treated with salvage RT and were retrospectively analyzed. The sites of the second OR were locoregional recurrence in 7 patients and distant metastasis in 14 patients. Salvage RT was performed at a median total dose of 60 Gy. Nineteen (90%) patients had an objective response. The median overall survival and progression-free survival (PFS) times were 41 and 24 months after salvage RT for the second OR, respectively. The 3-year local (in-field) control (LC) rates were 93%. The toxicities were mild; acute toxicities ≥Grade 3 were seen in one patient with Grade 3 dermatitis, and no late toxicity ≥Grade 2 was observed. In conclusion, salvage RT for the second OR was able to achieve a better LC rate and longer PFS time without inducing severe toxicity, and therefore may be a potentially effective modality for inducing long-term survival in select patients.

Enlarged perivascular spaces are associated with the disease activity in systemic lupus erythematosus.

To determine whether any brain MR abnormalities, including enlarged perivascular spaces (EPVS), were associated with disease activity in systemic lupus erythematosus (SLE) as an inflammatory activity. One hundred and thirty SLE patients with normal MR findings were assessed. With regard to MRI abnormalities, patients with brain atrophy and mild white matter hyperintensity (WMH) on T2WI were not excluded. The disease activity was assessed using the SLEDAI and the BILAG scores. The imaging characteristics included centrum semiovale EPVS (CS- EPVS) and basal ganglia EPVS on T2WI, WMH, and brain atrophy. We used univariate and multivariate logistic regression analyses to determine the clinical (vascular risk factors and blood examinations) and imaging characteristics that were associated with the disease activity of SLE. High CS-EPVS to be the only factor that was independently associated with the severity of the SLEDAI and BILAG scores (odds ratio [OR] 5.77; 95% confidence interval [CI] 2.21-15.00; p < 0.001 for the SLEDAI, and OR 2.64; 95% CI 1.03-6.74; p = 0.042 for the BILAG score). The CS-EPVS in the SLE patients are associated with the systemic disease activity, suggesting that CS- EPVS may be indicative of the reactive changes of the white matter due to the inflammatory activity.