Deep learning-based metastasis detection in patients with lung cancer to enhance reproducibility and reduce workload in brain metastasis screening with MRI: a multi-center study.

OBJECTIVES: To assess whether a deep learning-based system (DLS) with black-blood imaging for brain metastasis (BM) improves the diagnostic workflow in a multi-center setting. MATERIALS AND METHODS: In this retrospective study, a DLS was developed in 101 patients and validated on 264 consecutive patients (with lung cancer) having newly developed BM from two tertiary university hospitals, which performed black-blood imaging between January 2020 and April 2021. Four neuroradiologists independently evaluated BM either with segmented masks and BM counts provided (with DLS) or not provided (without DLS) on a clinical trial imaging management system (CTIMS). To assess reading reproducibility, BM count agreement between the readers and the reference standard were calculated using limits of agreement (LoA). Readers' workload was assessed with reading time, which was automatically measured on CTIMS, and were compared between with and without DLS using linear mixed models considering the imaging center. RESULTS: In the validation cohort, the detection sensitivity and positive predictive value of the DLS were 90.2% (95% confidence interval [CI]: 88.1-92.2) and 88.2% (95% CI: 85.7-90.4), respectively. The difference between the readers and the reference counts was larger without DLS (LoA: -0.281, 95% CI: -2.888, 2.325) than with DLS (LoA: -0.163, 95% CI: -2.692, 2.367). The reading time was reduced from mean 66.9 s (interquartile range: 43.2-90.6) to 57.3 s (interquartile range: 33.6-81.0) (P <.001) in the with DLS group, regardless of the imaging center. CONCLUSION: Deep learning-based BM detection and counting with black-blood imaging improved reproducibility and reduced reading time, on multi-center validation.

Perilesional and homotopic area activation during proverb comprehension after stroke.

INTRODUCTION: The mechanism of functional recovery in right hemisphere (RH) stroke patients when attempting to comprehend a proverb has not been identified. We previously reported that there is bilateral hemisphere involvement during proverb comprehension in the normal population. However, the underlying mechanisms of proverb comprehension following a right middle cerebral artery (MCA) infarction have not yet been fully elucidated. METHODS: We here compared the brain regions activated by literal sentences and by opaque or transparent proverbs in right MCA infarction patients using functional magnetic resonance imaging (fMRI). Experimental stimuli included 18 opaque proverbs, 18 transparent proverbs, and 18 literal sentences that were presented pseudorandomly in 1 of 3 predesigned sequences. RESULTS: Fifteen normal adults and 17 right MCA infarction patients participated in this study. The areas of the brain in the stroke patients involved in understanding a proverb compared with a literal sentence included the right middle frontal gyrus (MFG) and frontal pole, right anterior cingulate gyrus/paracingulate gyrus and left inferior frontal gyrus (IFG), middle temporal gyrus (MTG), precuneus, and supramarginal gyrus (SMG). When the proverbs were presented to these stroke patients in the comprehension tests, the left supramarginal, postcentral gyrus, and right paracingulate gyrus were activated for the opaque proverbs compared to the transparent proverbs. CONCLUSIONS: These findings suggest that the functional recovery of language in stroke patients can be explained by perilesional activation, which is thought to arise from the regulation of the excitatory and inhibitory neurotransmitter system, and by homotopic area activation which has been characterized by decreased transcallosal inhibition and astrocyte involvement.

Amide proton transfer imaging seems to provide higher diagnostic performance in post-treatment high-grade gliomas than methionine positron emission tomography.

OBJECTIVES: To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas. MATERIALS AND METHODS: This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNRmax and APTmax) and 90% histogram values (TNR90 and APT90). RESULTS: A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APTmax (AUC, 0.88) and APT90 (AUC, 0.78-0.83) had a similar to better diagnostic performance than TNRmax (AUC, 0.71, p = 0.08) or TNR90 (AUC, 0.53-0.59, p = 0.01-0.05). CONCLUSIONS: In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism. KEY POINTS: • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence.

Diffusion radiomics as a diagnostic model for atypical manifestation of primary central nervous system lymphoma: development and multicenter external validation.

Background: Radiomics is a rapidly growing field in neuro-oncology, but studies have been limited to conventional MRI, and external validation is critically lacking. We evaluated technical feasibility, diagnostic performance, and generalizability of a diffusion radiomics model for identifying atypical primary central nervous system lymphoma (PCNSL) mimicking glioblastoma. Methods: A total of 1618 radiomics features were extracted from diffusion and conventional MRI from 112 patients (training set, 70 glioblastomas and 42 PCNSLs). Feature selection and classification were optimized using a machine-learning algorithm. The diagnostic performance was tested in 42 patients of internal and external validation sets. The performance was compared with that of human readers (2 neuroimaging experts), cerebral blood volume (90% histogram cutoff, CBV90), and apparent diffusion coefficient (10% histogram, ADC10) using the area under the receiver operating characteristic curve (AUC). Results: The diffusion radiomics was optimized with the combination of recursive feature elimination and a random forest classifier (AUC 0.983, stability 2.52%). In internal validation, the diffusion model (AUC 0.984) showed similar performance with conventional (AUC 0.968) or combined diffusion and conventional radiomics (AUC 0.984) and better than human readers (AUC 0.825-0.908), CBV90 (AUC 0.905), or ADC10 (AUC 0.787) in atypical PCNSL diagnosis. In external validation, the diffusion radiomics showed robustness (AUC 0.944) and performed better than conventional radiomics (AUC 0.819) and similar to combined radiomics (AUC 0.946) or human readers (AUC 0.896-0.930). Conclusion: The diffusion radiomics model had good generalizability and yielded a better diagnostic performance than conventional radiomics or single advanced MRI in identifying atypical PCNSL mimicking glioblastoma.

Improved Diagnostic Accuracy of Alzheimer's Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer's Disease Neuroimaging Initiative Set.

OBJECTIVE: To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. MATERIALS AND METHODS: Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. RESULTS: Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). CONCLUSION: Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

Neural correlates of Korean proverb processing: A functional magnetic resonance imaging study.

INTRODUCTION: The Korean language is based on a syntactic system that is different from other languages. This study investigated the processing area of the Korean proverb in comparison with the literal sentence using functional magnetic resonance imaging. In addition, the effect of opacity and transparency of proverbs on the activation pattern, when familiarity is set to the same condition, was also examined. METHODS: The experimental stimuli included 36 proverbs and 18 literal sentences. A cohort of 15 healthy participants silently read each sentence for 6 s. A total of 18 opaque proverbs, 18 transparent proverbs, and 18 literal sentences were presented pseudo-randomly in one of three predesigned sequences. RESULTS: Compared with the literal sentences, a significant activation pattern was observed in the left hemisphere, including the left inferior frontal gyrus, in association with the proverbs. Compared with the transparent proverbs, opaque proverbs elicited more activation in the right supramarginal gyrus and precuneus. CONCLUSIONS: Our study confirmed that the left inferior frontal gyrus mediates the retrieval and/or selection of semantic knowledge in the Korean language. The present findings indicated that the right precuneus and the right supramarginal gyrus may be involved in abstract language processing.

Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: Multifactorial analysis in 385 patients.

PURPOSE: To determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations. MATERIALS AND METHODS: In this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student's t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy. RESULTS: The mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with ≥20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P < .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis. CONCLUSION: Multiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.

Differences in dynamic and static functional connectivity between young and elderly healthy adults.

PURPOSE: Brain connectivity is highly dynamic, but functional connectivity (FC) studies using resting-state functional magnetic resonance imaging (rs-fMRI) assume it to be static. This study assessed differences in dynamic FC between young healthy adults (YH) and elderly healthy adults (EH) compared to static FC. METHODS: Using rs-fMRI data from 12 YH and 31 EH, FC was assessed in six functional regions (subcortical, auditory [AUD], sensorimotor [SM], visuospatial [VS], cognitive control [CC], and default mode network [DMN]). Static FC was calculated as Fisher's z-transformed correlation coefficient. The sliding time window correlation (window size 30 s, step size 3 s) was applied for dynamic FC, and the standard deviation across sliding windows was calculated. Differences in static and dynamic FC between EH and YH were calculated and compared by region. RESULTS: EH showed decreased static FC in the subcortical, CC, and DMN regions (FDR corrected p = 0.0013; 74 regions), with no regions showing static FC higher than that in YH. EH showed increased dynamic FC in the subcortical, CC, and DMN regions, whereas decreased dynamic FC in CC and DMN regions (p < 0.01). However, the regions showing differences between EH and YH did not overlap between static and dynamic FC. CONCLUSION: Dynamic FC exhibited differences from static FC in EH and YH, mainly in regions involved in cognitive control and the DMN. Altered dynamic FC demonstrated both qualitatively and quantitatively distinct patterns of transient brain activity and needs to be studied as an imaging biomarker in the aging process.

Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson's disease.

BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.

Relationship between clinical phenotypes and cognitive impairment in Parkinson's disease (PD).

Most patients with idiopathic PD (IPD) show variable degrees of cognitive decline. The purpose of this study was to evaluate the relationship between the predominant motor symptom at the time of disease onset and the level of cognitive function in patients with IPD. A total of 159 patients with IPD were enrolled in this study. The patients' initial motor symptoms were classified into three types: tremor-dominant (TD), bradykinesia and rigidity-dominant (BRD), gait and postural instability-dominant (GPD). Disease severity was rated according to the Hoehn-Yahr classification (H&Y stage). Overall cognitive status was evaluated using the Korean versions of the Mini-Mental State Examination (K-MMSE) and the Modified Mini-Mental State (3MS) tests. The GPD group showed the lowest scores of the K-MMSE/3MS, and the patients with TD showed the best performance in the cognitive analysis (p<0.05). The patients who were older at disease onset showed worse cognitive performance than those the patients who were younger at disease onset (p<0.05). There was no difference in cognitive status according to H&Y stages. The accurate classification of initial motor symptoms and the detailed history, including the exact onset age of IPD, may allow us to predict cognitive decline in IPD.

Establishment of an indocyanine green test using an automatic chemistry analyzer.

The indocyanine green (ICG) clearance test has been used to assess the reserve of hepatic function. This method is based on the spectrometric measurement of its plasma concentration at maximum wavelength of 805 nm, which requires a spectrophotometer and associated maintenance. We established an ICG clearance test using a Toshiba 200FR automatic chemistry analyzer that can be tuned to a wavelength of approximately 805 nm. Five pooled sera spiked from 0 to 4.0 mg/dL were analyzed for linearity test and precision was determined at five levels in the range 0.1-2.0 mg/dL. The ICG retention rate at 15 min (R15) was determined for 38 patients using a conventional method and our method. The ICG clearance test using the automatic chemistry analyzer showed good linearity, and precision ranged from 0.3% to 1.0% for within-run CVs and from 0.6% to 4.7% for total CVs. The degree of agreement between the two methods was also acceptable (mean difference of 1.5%). It is expected that the ICG test using the automatic chemistry analyzer can replace the conventional ICG clearance test, considering the excellent agreement, good precision and linearity over a clinically relevant range.