Background and Objectives:The glymphatic system is a whole-brain perivascular network, which promotes CSF/interstitial fluid exchange. Alterations to this system may play a pivotal role in amyloid β (Aβ) accumulation. However, its involvement in Alzheimer’s disease (AD) pathogenesis is not fully understood. Here, we investigated the changes in noninvasive MRI measurements related to the perivascular network in patients with mild cognitive impairment (MCI) and AD. Additionally, we explored the associations of MRI measures with neuropsychological score, PET standardized uptake value ratio (SUVR), and Aβ deposition.Methods:MRI measures, including perivascular space (PVS) volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM), and index of diffusivity along the perivascular space (ALPS index) of patients with MCI, those with AD, and healthy controls from the Alzheimer’s Disease Neuroimaging Initiative database were compared. MRI measures were also correlated with the levels of CSF biomarkers, PET SUVR, and cognitive score in the combined subcohort of patients with MCI and AD. Statistical analyses were performed with age, sex, years of education, and APOE status as confounding factors.Results:In total, 36 patients with AD, 44 patients with MCI, and 31 healthy controls were analyzed. Patients with AD had significantly higher total, WM, and basal ganglia PVSVF (Cohen’s d = 1.15-1.48; p < 0.001), and FW-WM (Cohen’s d = 0.73; p < 0.05) and a lower ALPS index (Cohen’s d = 0.63; p < 0.05) than healthy controls. Meanwhile, the MCI group only showed significantly higher total (Cohen’s d = 0.99; p < 0.05) and WM (Cohen’s d = 0.91; p < 0.05) PVSVF. Low ALPS index was associated with lower CSF Aβ42 (rs = 0.41, pfdr = 0.026), FDG-PET uptake (rs = 0.54, pfdr < 0.001), and worse multiple cognitive domain deficits. High FW-WM was also associated with lower CSF Aβ42 (rs = −0.47, pfdr = 0.021) and worse cognitive performances.Conclusion:Our study indicates that changes in PVS-related MRI parameters occur in MCI and AD, possibly due to impairment of the glymphatic system. We also report the associations between MRI parameters and Aβ deposition, neuronal change, and cognitive impairment in AD.

We aimed to evaluate a computer-aided diagnosis (CADx) system for lung nodule classification focussing on (i) usefulness of the conventional CADx system (hand-crafted imaging feature + machine learning algorithm), (ii) comparison between support vector machine (SVM) and gradient tree boosting (XGBoost) as machine learning algorithms, and (iii) effectiveness of parameter optimization using Bayesian optimization and random search. Data on 99 lung nodules (62 lung cancers and 37 benign lung nodules) were included from public databases of CT images. A variant of the local binary pattern was used for calculating a feature vector. SVM or XGBoost was trained using the feature vector and its corresponding label. Tree Parzen Estimator (TPE) was used as Bayesian optimization for parameters of SVM and XGBoost. Random search was done for comparison with TPE. Leave-one-out cross-validation was used for optimizing and evaluating the performance of our CADx system. Performance was evaluated using area under the curve (AUC) of receiver operating characteristic analysis. AUC was calculated 10 times, and its average was obtained. The best averaged AUC of SVM and XGBoost was 0.850 and 0.896, respectively; both were obtained using TPE. XGBoost was generally superior to SVM. Optimal parameters for achieving high AUC were obtained with fewer numbers of trials when using TPE, compared with random search. Bayesian optimization of SVM and XGBoost parameters was more efficient than random search. Based on observer study, AUC values of two board-certified radiologists were 0.898 and 0.822. The results show that diagnostic accuracy of our CADx system was comparable to that of radiologists with respect to classifying lung nodules.

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PurposeThe dopamine hypothesis suggests that excessive dopamine release results in the symptoms of schizophrenia. The purpose of this study was to elucidate the dopaminergic and noradrenergic neurons using 3-T neuromelanin magnetic resonance imaging (MRI) in patients with schizophrenia and healthy control subjects.MethodsWe prospectively examined 52 patients with schizophrenia (M: F = 27∶25, mean age, 35 years) and age- and sex-matched healthy controls. Using a 3T MRI unit, we obtained oblique T1-weighted axial images perpendicular to the brainstem. We measured the signal intensity and area for the substantia nigra (SNc), midbrain tegmentum, locus ceruleus (LC), and pons. We then calculated the contrast ratios (CR) for the SNc (CRSN) and LC (CRLC), which were compared between patients and healthy controls using unpaired t-tests.ResultsThe SNc and LC were readily identified in both patients and healthy controls as areas with high signal intensities in the posterior part of the cerebral peduncle and in the upper pontine tegmentum. The CRSN values in patients were significantly higher than those in healthy controls (10.89±2.37 vs. 9.6±2.36, p<0.01). We observed no difference in the CRLC values between the patients and healthy controls (14.21±3.5 vs. 13.44±3.37, p = 0.25). Furthermore, there was no difference in area of the SNc and LC between schizophrenia patients and controls.ConclusionsNeuromelanin MRI might reveal increased signal intensity in the SNc of patients with schizophrenia. Our results indicate the presence of excessive dopamine products in the SNc of these patients.

Impalred baroreflex function 1s a factor responslble for poor prognosis m myocardlal infarction patients Usmg loglstlc function curves, we calculated the maximal gam of the baroreflex control of renal sympathetic nerve actlvlty (RSNA) and heart rate m conscious Wlstar-Kyoto and spontaneously hypertensive rats whose left anterior descending artery had been ligated 4 weeks earlier We further investigated whether 3-week oral treatment with the anglotensm II type 1 receptor antagonist TCV-116 would Improve the baroreflex m rats with myocardlal infarction The maximal gam of the mean arterial pressure-RSNA relation m spontaneously hypertensive rats with myocardlal mfarctlon and treated with vehicle (1 7tO 1% control per mm Hg) was smaller than the gam m sham-operated hypertensive rats (2 3-+0 1% control per mm Hg) After 3-week oral treatment with TCV-I 16, the maximal gam of the arterial pressure-RSNA relation in hypertensive rats with myocardlal I t has been reported that baroreflex function 1s lmpaired in hypertension, I-? that MI 1s associated with an impaired baroreflex, and that the blunted baroreflex in MI IS involved m sudden death or fatal arrhythmia 4-h Recently, It has been reported that mtravenously injected Ang II receptor antagonist improves the blunted baroreflex m MI In normotensive rats7 and that lmprovement in baroreflex by blockade of the remn-anglotensm system has a favorable influence on the long-term outcome of patients with Ml 5,*,Q Thus, baroreflex dysfunction 1s considered a crltlcal factor in the poor prognosis of MI patients Moreover, smce a recent study examining the relation between blood pressure and mortality among men with prior MI showed that the percentage of men dymg from coronary artery disease was much higher In the hypertensive group, 10 It 1s important to examme whether high blood pressure exacerbates the influence of MI on baroreflex functionIn the present study, we compared the baroreflex function of conscious WKY and SHR whose left coronary artery had been ligated 4 weeks earher We also tested the hypothesis that long-term oral treatment with the Ang II receptor antagonist TCV-116 would improve the baroreflex controls of RSNA and HR m WKY and SHR with MI MethodsMale IS-week-old SHR and age-matched WKY were purchased from Charles River Japan Co, Atsugi, Japan All surglcal and experimental procedures were m accordance with institutional dmmal care gmdelmes Rats were housed singly m cages m a room with constant temperature and a 12-hour light/dark cycle Myocardial InfarctionWe used a previously described technique' 11 13 involving IIgatlon of the left coronary artery to produce chronic MI With rats under ether inhalation anesthesia, the heart was exteriorized via a left thoracotomy, and the left antenor descending artery was ligated between the pulmonary outflow tract and left atrium The heart was returned to Its normal position, the thorax was closed, and the an was removed Sham control rats underwent the same procedure but did not have then left coronary artery ligated ...

This study was conducted to clarify the mechanisms of body nitrogen losses according to the severity of surgical trauma. Thirteen male patients who underwent operation for esophageal cancer (group E), and 11 men (who underwent gastric or colorectal surgeries (group GC) were studied. The measurement of whole-body protein turnover, synthesis, and breakdown were made preoperatively on the 3rd and 10th postoperative day with constant infusion of [ 15 N]glycine during isocaloric and isonitrogenous total parenteral nutrition. Significant increases in the rates of whole-body protein turnover (flux) and breakdown were seen in group E on the 3rd postoperative day (p < 0.01, p < 0.01, respectively), whereas the increases were not significant in group GC. The rates of wholebody protein flux and breakdown were significantly greater in group E than group GC (p < 0.01, p < 0.01, respectively). The rate of protein synthesis significantly increased in group E (p < 0.05), but did not alter or slightly decreased in group GC. The rates of whole-body protein flux and breakdown in group E were still significantly greater on the 10th postoperative day than preoperatively. It was concluded that unchanged or slightly decreased rates of whole-body protein synthesis with slightly increased breakdown were seen in the group of patients who underwent gastric or colorectal surgery, whereas synthesis increased significantly with a greater increase of breakdown in patients receiving severe surgical procedures, esophagectomy for esophageal cancer. (Journal of Parenteral and Enteral Nutrition 15:169-172, 1991) The mechanisms underlying the protein catabolic response to injury are still not thoroughly understood. It has been generally assumed that hypercatabolic nitrogen losses, as originally described by Cuthbertsonl are due to the increased protein catabolism. However, O'Keefe et al' and later Crane et al3 have challenged this view with their findings of decreased protein synthetic and unchanged breakdown rates following elective surgery. In contrast, Long et al4 and Kien et al5 reported the contrary results.To clarify these discrepancies in the literature with regard to changes in protein metabolism following surgical stress, we have compared the dynamics of protein metabolism between patient group who underwent surgery for esophageal cancer and patient group receiving gastric or colorectal surgery, using a constant infusion of (15N]glycine, according to the method of Picou and Taylor-Roberts.' 6 MATERIALS AND METHODSThe clinical detail of the patients were shown in Tables I and II. Group E consisted of 13 male patients who received resection of thoracic esophagus for esophageal cancer with cervical, mediastinal, and intraabdominal lymphnodes dissection followed by reconstruction using gastric tube or colon through retrosternal route. Group GC consisted of 11 male patients who underwent total gastrectomy, hemicolectomy, or low anterior resection for gastric or colorectal cancer. All patients had normal hepatic and renal function and were no...

A mere 10-s difference in scan timing could make a difference on prevalence and diagnostic performance of the CTA spot sign, suggesting a need for the standardization of the CTA protocol to generalize the approach for effective clinical application.

Along with arterial blood pressure reduction, maintenance of the integrity of baroreceptor reflex function contributes to preserving end-organ function in the treatment of hypertensive patients. The purpose of this study was to investigate the effects of antihypertensive agents (trichlormethiazide, atenolol, nicardipine, and enalapril) on baroreceptor reflex function by comparing early and late starts of treatment. We administered each agent to spontaneously hypertensive rats (SHR) as early-start groups from 10 to 36 weeks of age and as late-start groups from 28 to 36 weeks of age. We evaluated the gain of the reflex control of renal sympathetic nerve activity and heart rate using ramp infusions of phenylephrine and nitroglycerin in untreated SHR at 10, 28, or 36 weeks of age and in treated SHR at 36 weeks of age. In 28- and 36-week-old untreated SHR, the renal sympathetic nerve activity gain was not altered and the heart rate gain was decreased (from -2.3 +/- 0.3 to -1.3 +/- 0.3 and -1.2 +/- 0.3 beats per minute [bm]/mm Hg, P < .05, respectively) compared with 10-week-old SHR. Early and late start of therapy produced arterial pressure reductions (-18 +/- 4 and -12 +/- 5 mm Hg, P < .05, respectively). In the early-start groups, the renal sympathetic nerve activity gain was improved markedly in nicardipine- and enalapril-treated SHR (-4.2 +/- 0.2% and -4.9 +/- 0.2% of control/mm Hg, P < .01, respectively), and the heart rate gain was improved markedly in atenolol- and enalapril-treated SHR (-4.1 +/- 0.2 and -4.4 +/- 0.2 bpm/mm Hg, P < .01, respectively). In the late-start groups, the renal sympathetic nerve activity gain was improved moderately in nicardipine- and enalapril-treated SHR (-3.8 +/- 0.2% and -2.9 +/- 0.2% of control/mm Hg, P < .05, respectively). The heart rate gain was improved slightly only in nicardipine-treated SHR (-1.9 +/- 0.2 bpm/mm Hg, P < .05). These results demonstrate that an early start of antihypertensive treatment improves baroreceptor reflex function markedly compared with a late start of treatment. This supports the hypothesis that a possible critical phase sensitive to intervention with antihypertensive treatment exists during the development of hypertension and indicates that the early start of antihypertensive treatment would be required in clinical practice.