Monitoring of metastatic progression by CE-HFUS with Als.

<p>A. Imaging of the temporal changes in angiogenic vessel density in a cross-section of a metastatic proper-ALN, visualized by CE-HFUS with ALs. Blood vessel density increased with tumor progression. Red circles indicate the proper-ALN boundary, arrows and dotted lines indicate the AL-enhanced region, and green highlighting indicates the dense area of neovasculature in the proper-ALN. B. Results of 3D quantitative analysis of the temporal changes in blood vessel volume and density in metastatic proper-ALNs. The term “cells” indicates the metastasized group (1×10⁵ cells/min, <i>n</i> = 4) and “PBS” the negative control group (<i>n</i> = 3). Values for each group were normalized against the measurement on day 0. Error bars indicate the SEM values. * is for comparison of the temporal change within each group; # is for comparison between groups. * or #, <i>P</i><0.05; ** or ##, <i>P</i><0.01, calculated using two-way ANOVA followed by the Tukey-Kramer test.</p

Establishment of the model of lymph node metastasis.

<p>A. Representative images captured by <i>in vivo</i> bioluminescence imaging of a mouse with tumor cells grafted into the SiLN to promote metastasis to the ALN. (<i>a</i>) <i>In vivo</i> and (<i>b</i>) <i>ex vivo</i> bioluminescence signals in the proper-ALN and SiLN on day 14 post-inoculation, indicating that the proper-ALN is the draining lymph node. B. Graph showing the high correlation between <i>in vivo</i> and <i>ex vivo</i> bioluminescence (<i>P</i> = 0.0023; Spearman’s rank correlation coefficient [rs]  = 0.9161; SiLN, <i>n</i> = 6; proper-ALN, <i>n</i> = 6). C. Results of histological verification. Tumor cells stained with H&E and luciferase-positive immunohistochemical signals in the proper-ALN and SiLN. MS: marginal sinus. T: tumor. D. Dissemination of KM-Luc/GFP cells (metastasis, <i>n = </i>4) or PBS alone (control, <i>n = </i>3) to each organ, assessed on day 14 post-injection of the SiLN. I, ipsilateral; C, contralateral; LN, lymph node. Error bars indicate the SEM values.</p

Metastatic flow and route. A.

<p>ICG flow from the SiLN to the proper-ALN, observed using an <i>in vivo</i> fluorescence imaging system (IVIS; <i>n</i> = 1). <b>B.</b> Representative PDE images, following an ICG injection speed of 0.5 mL/h. The speed of ICG flow was calculated by dividing the distance, <i>l</i>, by the duration of time that had elapsed post-injection. <b>C.</b> Graph of the relationship between ICG flow speed and intra-SiLN injection speed (low, 0.5; medium, 1.0; high, 3.0 mL/h; <i>n</i> = 4 per group), revealing a low level of variation between individual experiments in the low-speed group. D. HS-FVCS image of the afferent lymphatic vessels after intra-SiLN injection of FITC-BSA solution (<i>n</i> = 2). (<i>a</i>) Area near the SiLN and proper-ALN captured by a normal digital camera. Two regions of interest were selected. (<i>b</i>) Bright field images obtained by HS-FVCS, without use of a fluorescence filter. A thick superficial epigastric vein (→) was observed. (<i>c</i>) Fluorescence images obtained by HS-FVCS, with use of an appropriate fluorescence filter (bandwidth: 510±2 nm). A new flow channel filled with FITC-BSA solution (→) appeared at a distance of about 200 µm from the vein. (<i>d</i>) Results of hematoxylin and eosin (H&E) staining. The flow channel was identified as the afferent lymphatic vessels by injection of Indian ink. The vein was not stained (<i>n</i> = 1).</p

Results of the whole-brain voxel-based analyses.

<p>First row: The brain regions that exhibited regional cerebral glucose metabolic reductions in the 60 PD patients relative to 14 normal volunteers (p<0.05 uncorrected, extent threshold of 100 voxels). Second row and below: The brain regions in which the resting CMRglc was correlated with the RTs in the various psychophysical tasks (Global: second row, Local: third row, Mixed: fourth row) and the shift cost (fifth row) (<i>p</i><0.001 uncorrected, extent threshold of 100 voxels). PD, Parkinson’s disease; R, right; L, left.</p

Representative cases with and without silent brain infarction.

<p>Above: 63-year-old man without silent brain infarction (SBI). Below: 61-year-old man with SBI. Left: magnetic resonance images; middle: laser speckle flowgraphy (LSFG) color maps; right: LSFG-measured mean blur rate (MBR) waveform. The arrows in the MRI images for the SBI case show regions of clearly visible SBI. The ellipse indicates the optic nerve head (ONH) margin. The LSFG software automatically divided the overall ONH into large vessel and capillary areas. The MBR waveform for the SBI case show that the peak of the waveform is steeper and has a more clearly defined peak than the non-SBI case, which may reflect the effect of age-related vascular changes on the MBR waveform. Furthermore, the values for BOT are 56.5 and 41.6 arbitrary units in the SBI and non-SBI cases, respectively.</p

Demographic and clinical characteristics of patients with PD and control participants.

<p>PD, Parkinson’s disease; MMSE, Mini Mental State Examination; CDR, Clinical Dementia Rating; NPI, Neuropsychiatric Inventory; UPDRS-III, Unified Parkinson’s Disease Rating Scale-motor score; L, left; R, right; B, bilateral.</p

Schematic illustrations of the psychophysical tasks.

<p>In both the Global and Local tasks, compound letter stimuli appeared after a 2-second presentation of a visual cue that indicated whether the target was a global or local letter. The subjects were instructed to respond orally to the target component of each compound letter stimulus as quickly as possible. In these tasks, the subjects maintained their attention on a single component of the compound letters (either the local or global component of the stimuli), and they were not required to reorient their attention. However, in the Mixed task, the cue that indicated the target component of the compound letter changed from trial to trial in a pseudorandom manner. The task required that the subjects switch their attention on the basis of the cue that was presented to them on each trial.</p

Logistic regression analysis of independent variables affecting the presence of silent brain infarction in primary aldosteronism patients.

<p>SBP = systolic blood pressure, U = urinary</p><p>PRA = plasma renin activity, SBI = silent brain infarction,</p><p>HDL-C = high-density lipoprotein cholesterol, PAC = plasma aldosterone concentration,</p><p>eGFR = estimated glomerular filtration rate,</p><p>OR: odds ratio, CI: confidence interval.</p><p>Logistic regression analysis of independent variables affecting the presence of silent brain infarction in primary aldosteronism patients.</p

The results of the ROI-based stepwise multiple regression analyses.

<p>7 ROIs are shown in different colors: right DLPFC  =  red, left DLPFC  =  cyan, left VLPFC  =  yellow, right TPO  =  purple, left TPO  =  green, medial parietal cortex  =  white, and left posterior IT  =  blue. The scatterplots illustrate the relationship between the psychophysical task performance scores and the FDG-uptake values in the ROIs. DLPFC, dorsolateral prefrontal cortex; VLPFC, ventrolateral prefrontal cortex; TPO, temporo-parieto-occipital junction; posterior IT, posterior inferior temporal cortex; FDG, ¹⁸F-fluorodeoxyglucose.</p