Structural neuroimaging changes associated with subjective cognitive decline from a clinical sample.

BACKGROUND: Alzheimer's disease (AD) is characterized by progressive deterioration of cognitive functions. Some individuals with subjective cognitive decline (SCD) are in the early phase of the disease and subsequently progress through the AD continuum. Although neuroimaging biomarkers could be used for the accurate and early diagnosis of preclinical AD, the findings in SCD samples have been heterogeneous. This study established the morphological differences in brain magnetic resonance imaging (MRI) findings between individuals with SCD and those without cognitive impairment based on a clinical sample of patients defined according to SCD-Initiative recommendations. Moreover, we investigated baseline structural changes in the brains of participants who remained stable or progressed to mild cognitive impairment or dementia. METHODS: This study included 309 participants with SCD and 43 healthy controls (HCs) with high-quality brain MRI at baseline. Among the 99 subjects in the SCD group who were followed clinically, 32 progressed (SCDp) and 67 remained stable (SCDnp). A voxel-wise statistical comparison of gray and white matter (WM) volume was performed between the HC and SCD groups and between the HC, SCDp, and SCDnp groups. XTRACT ATLAS was used to define the anatomical location of WM tract damage. Region-of-interest (ROI) analyses were performed to determine brain volumetric differences. White matter lesion (WML) burden was established in each group. RESULTS: Voxel-based morphometry (VBM) analysis revealed that the SCD group exhibited gray matter atrophy in the middle frontal gyri, superior orbital gyri, superior frontal gyri, right rectal gyrus, whole occipital lobule, and both thalami and precunei. Meanwhile, ROI analysis revealed decreased volume in the left rectal gyrus, bilateral medial orbital gyri, middle frontal gyri, superior frontal gyri, calcarine fissure, and left thalamus. The SCDp group exhibited greater hippocampal atrophy (p < 0.001) than the SCDnp and HC groups on ROI analyses. On VBM analysis, however, the SCDp group exhibited increased hippocampal atrophy only when compared to the SCDnp group (p < 0.001). The SCD group demonstrated lower WM volume in the uncinate fasciculus, cingulum, inferior fronto-occipital fasciculus, anterior thalamic radiation, and callosum forceps than the HC group. However, no significant differences in WML number (p = 0.345) or volume (p = 0.156) were observed between the SCD and HC groups. CONCLUSIONS: The SCD group showed brain atrophy mainly in the frontal and occipital lobes. However, only the SCDp group demonstrated atrophy in the medial temporal lobe at baseline. Structural damage in the brain regions was anatomically connected, which may contribute to early memory decline.

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Comparison of Myocardial Blood Flow Quantification Models for Double ECG Gating Arterial Spin Labeling MRI: Reproducibility Assessment.

BACKGROUND: Arterial spin labeling (ASL) allows non-invasive quantification of myocardial blood flow (MBF). Double-ECG gating (DG) ASL is more robust to heart rate variability than single-ECG gating (SG), but its reproducibility requires further investigation. Moreover, the existence of multiple quantification models hinders its application. Frequency-offset-corrected-inversion (FOCI) pulses provide sharper edge profiles than hyperbolic-secant (HS), which could benefit myocardial ASL. PURPOSE: To assess the performance of MBF quantification models for DG compared to SG ASL, to evaluate their reproducibility and to compare the effects of HS and FOCI pulses. STUDY TYPE: Prospective. SUBJECTS: Sixteen subjects (27 ± 8 years). FIELD STRENGTH/SEQUENCE: 1.5 T/DG and SG flow-sensitive alternating inversion recovery ASL. ASSESSMENT: Three models for DG MBF quantification were compared using Monte Carlo simulations and in vivo experiments. Two models used a fitting approach (one using only a single label and control image pair per fit, the other using all available image pairs), while the third model used a T1 correction approach. Slice profile simulations were conducted for HS and FOCI pulses with varying B0 and B1. Temporal signal-to-noise ratio (tSNR) was computed for different acquisition/quantification strategies and inversion pulses. The number of images that minimized MBF error was investigated in the model with highest tSNR. Intra and intersession reproducibility were assessed in 10 subjects. STATISTICAL TESTS: Within-subject coefficient of variation, analysis of variance. P-value <0.05 was considered significant. RESULTS: MBF was not different across acquisition/quantification strategies (P = 0.27) nor pulses (P = 0.9). DG MBF quantification models exhibited significantly higher tSNR and superior reproducibility, particularly for the fitting model using multiple images (tSNR was 3.46 ± 2.18 in vivo and 3.32 ± 1.16 in simulations, respectively; wsCV = 16%). Reducing the number of ASL pairs to 13/15 did not increase MBF error (minimum = 0.22 mL/g/min). DATA CONCLUSION: Reproducibility of MBF was better for DG than SG acquisitions, especially when employing a fitting model. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Diagnostic and Prognostic Potential of Multiparametric Renal MRI in Kidney Transplant Patients.

BACKGROUND: Multiparametric MRI provides assessment of functional and structural parameters in kidney allografts. It offers a non-invasive alternative to the current reference standard of kidney biopsy. PURPOSE: To evaluate the diagnostic and prognostic utility of MRI parameters in the assessment of allograft function in the first 3-months post-transplantation. STUDY TYPE: Prospective. SUBJECTS: 32 transplant recipients (54 ± 17 years, 20 females), divided into two groups according to estimated glomerular filtration rate (eGFR) at 3-months post-transplantation: inferior graft function (IGF; eGFR<45 mL/min/1.73 m2 , n = 10) and superior graft function (SGF; eGFR ≥ 45 mL/min/1.73 m2 , n = 22). Further categorization was based on the need for hemodialysis (C1) and decrease in s-creatinine (C2) at 1-week post-transplantation: delayed-graft-function (DGF: n = 4 C1, n = 10 C2) and early graft-function (EGF: n = 28 C1, n = 22 C2). FIELD STRENGTH/SEQUENCE: 3-T, pseudo-continuous arterial spin labeling, T1-mapping, and diffusion-weighted imaging. ASSESSMENT: Multiparametric MRI was evaluated at 1-week in all patients and 3-months after transplantation in 28 patients. Renal blood flow (RBF), diffusion coefficients (ADC, ΔADC, D, ∆ $$ \Delta $$ D, D*, flowing fraction f), T1 and ∆ $$ \Delta $$ T1 were calculated in cortex and medulla. The diagnostic and prognostic value of these parameters, obtained at 3-months and 1-week post-transplantation, respectively, was evaluated in the cortex to discriminate between DGF and EGF, and between SGF and IGF. STATISTICAL TESTS: Logistic regression, receiver-operating-characteristics, area-under-the-curve (AUC), confidence intervals (CIs), analysis-of-variance, t-test, Wilcoxon-Mann-Whitney test, Fisher's exact test, Pearson's correlation. P-value<0.05 was considered significant. RESULTS: DGF patients exhibited significantly lower cortical RBF and f and higher D*. The diagnostic value of MRI for detecting DGF was excellent (AUC = 100%). Significant differences between patients with IGF and SGF were found in RBF, ∆T1 , and ∆D. Multiparametric MRI showed higher diagnostic (AUC = 95.32%; CI: 88%-100%) and prognostic (AUC = 97.47%, CI: 92%-100%) values for detecting IGF than eGFR (AUC = 89.50%, CI: 79%-100%). DATA CONCLUSION: Multiparametric MRI may show high diagnostic and prognostic value in transplanted patients, yielding better results compared to eGFR measurements. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Validation of a new 3D quantitative BOLD based cerebral oxygen extraction mapping.

Quantitative BOLD (qBOLD) MRI allows evaluation of oxidative metabolism of the brain based purely on an endogenous contrast mechanism. The method quantifies deoxygenated blood volume (DBV) and hemoglobin oxygen saturation level of venous blood (Yv), yielding oxygen extraction fraction (OEF), and along with a separate measurement of cerebral blood flow, cerebral metabolic rate of oxygen (CMRO2) maps. Here, we evaluated our recently reported 3D qBOLD method that rectifies a number of deficiencies in prior qBOLD approaches in terms of repeat reproducibility and sensitivity to hypercapnia on the metabolic parameters, and in comparison to dual-gas calibrated BOLD (cBOLD) MRI for determining resting-state oxygen metabolism. Results suggested no significant difference between test-retest qBOLD scans in either DBV and OEF. Exposure to hypercapnia yielded group averages of 38 and 28% for OEF and 151 and 146 µmol/min/100 g for CMRO2 in gray matter at baseline and hypercapnia, respectively. The decrease of OEF during hypercapnia was significant (p ≪ 0.01), whereas CMRO2 did not change significantly (p = 0.25). Finally, baseline OEF (37 vs. 39%) and CMRO2 (153 vs. 145 µmol/min/100 g) in gray matter using qBOLD and dual-gas cBOLD were found to be in good agreement with literature values, and were not significantly different from each other (p > 0.1).

ASL lexicon and reporting recommendations: A consensus report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

The 2015 consensus statement published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group and the European Cooperation in Science and Technology ( COST) Action ASL in Dementia aimed to encourage the implementation of robust arterial spin labeling (ASL) perfusion MRI for clinical applications and promote consistency across scanner types, sites, and studies. Subsequently, the recommended 3D pseudo-continuous ASL sequence has been implemented by most major MRI manufacturers. However, ASL remains a rapidly and widely developing field, leading inevitably to further divergence of the technique and its associated terminology, which could cause confusion and hamper research reproducibility. On behalf of the ISMRM Perfusion Study Group, and as part of the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI), the ASL Lexicon Task Force has been working on the development of an ASL Lexicon and Reporting Recommendations for perfusion imaging and analysis, aiming to (1) develop standardized, consensus nomenclature and terminology for the broad range of ASL imaging techniques and parameters, as well as for the physiological constants required for quantitative analysis; and (2) provide a community-endorsed recommendation of the imaging parameters that we encourage authors to include when describing ASL methods in scientific reports/papers. In this paper, the sequences and parameters in (pseudo-)continuous ASL, pulsed ASL, velocity-selective ASL, and multi-timepoint ASL for brain perfusion imaging are included. However, the content of the lexicon is not intended to be limited to these techniques, and this paper provides the foundation for a growing online inventory that will be extended by the community as further methods and improvements are developed and established.

Automatic Segmentation and Quantification of Nigrosome-1 Neuromelanin and Iron in MRI: A Candidate Biomarker for Parkinson's Disease.

BACKGROUND: There is a lack of automated tools for the segmentation and quantification of neuromelanin (NM) and iron in the nigrosome-1 (N1). Existing tools evaluate the N1 sign, i.e., the presence or absence of the "swallow-tail" in iron-sensitive MRI, or globally analyze the MRI signal in an area containing the N1, without providing a volumetric delineation. PURPOSE: Present an automated method to segment the N1 and quantify differences in N1's NM and iron content between Parkinson's disease (PD) patients and healthy controls (HCs). Study whether N1 degeneration is clinically related to PD and could be used as a biomarker of the disease. STUDY TYPE: Prospective. SUBJECTS: Seventy-one PD (65.3 ± 10.3 years old, 34 female/37 male); 30 HC (62.7 ± 7.8 years old, 17 female/13 male). FIELD STRENGTH/SEQUENCE: 3 T Anatomical T1-weighted MPRAGE, NM-MRI T1-weighted gradient with magnetization transfer, susceptibility-weighted imaging (SWI). ASSESSMENT: N1 was automatically segmented in SWI images using a multi-image atlas, populated with healthy N1 structures manually annotated by a neurologist. Relative NM and iron content were quantified and their diagnostic performance assessed and compared with the substantia nigra pars compacta (SNc). The association between image parameters and clinically relevant variables was studied. STATISTICAL TESTS: Nonparametric tests were used (Mann-Whitney's U, chi-square, and Friedman tests) at P = 0.05. RESULTS: N1's relative NM content decreased and relative iron content increased in PD patients compared with HCs (NM-CRHC = 22.55 ± 1.49; NM-CRPD = 19.79 ± 1.92; NM-nVolHC = 2.69 × 10-5 ± 1.02 × 10-5 ; NM-nVolPD = 1.18 × 10-5 ± 0.96 × 10-5 ; Iron-CRHC = 10.51 ± 2.64; Iron-CRPD = 19.35 ± 7.88; Iron-nVolHC = 0.72 × 10-5 ± 0.81 × 10-5 ; Iron-nVolPD = 2.82 × 10-5 ± 2.04 × 10-5 ). Binary logistic regression analyses combining N1 and SNc image parameters yielded a top AUC = 0.955. Significant correlation was found between most N1 parameters and both disease duration (ρNM-CR = -0.31; ρiron-CR = 0.43; ρiron-nVol = 0.46) and the motor status (ρNM-nVol = -0.27; ρiron-CR = 0.33; ρiron-nVol = 0.28), suggesting NM reduction along with iron accumulation in N1 as the disease progresses. DATA CONCLUSION: This method provides a fully automatic N1 segmentation, and the analyses performed reveal that N1 relative NM and iron quantification improves diagnostic performance and suggest a relative NM reduction along with a relative iron accumulation in N1 as the disease progresses. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

A deep learning image analysis method for renal perfusion estimation in pseudo-continuous arterial spin labelling MRI.

Accurate segmentation of renal tissues is an essential step for renal perfusion estimation and postoperative assessment of the allograft. Images are usually manually labeled, which is tedious and prone to human error. We present an image analysis method for the automatic estimation of renal perfusion based on perfusion magnetic resonance imaging. Specifically, non-contrasted pseudo-continuous arterial spin labeling (PCASL) images are used for kidney transplant evaluation and perfusion estimation, as a biomarker of the status of the allograft. The proposed method uses machine/deep learning tools for the segmentation and classification of renal cortical and medullary tissues and automates the estimation of perfusion values. Data from 16 transplant patients has been used for the experiments. The automatic analysis of differentiated tissues within the kidney, such as cortex and medulla, is performed by employing the time-intensity-curves of non-contrasted T1-weighted MRI series. Specifically, using the Dice similarity coefficient as a figure of merit, results above 93%, 92% and 82% are obtained for whole kidney, cortex, and medulla, respectively. Besides, estimated cortical and medullary perfusion values are considered to be within the acceptable ranges within clinical practice.

Time discrimination and change detection could share a common brain network: findings of a task-based fMRI study.

Introduction: Over the past few years, several studies have described the brain activation pattern related to both time discrimination (TD) and change detection processes. We hypothesize that both processes share a common brain network which may play a significant role in more complex cognitive processes. The main goal of this proof-of-concept study is to describe the pattern of brain activity involved in TD and oddball detection (OD) paradigms, and in processes requiring higher cognitive effort. Methods: We designed an experimental task, including an auditory test tool to assess TD and OD paradigms, which was conducted under functional magnetic resonance imaging (fMRI) in 14 healthy participants. We added a cognitive control component into both paradigms in our test tool. We used the general linear model (GLM) to analyze the individual fMRI data images and the random effects model for group inference. Results: We defined the areas of brain activation related to TD and OD paradigms. We performed a conjunction analysis of contrast TD (task > control) and OD (task > control) patterns, finding both similarities and significant differences between them. Discussion: We conclude that change detection and other cognitive processes requiring an increase in cognitive effort require participation of overlapping functional and neuroanatomical components, suggesting the presence of a common time and change detection network. This is of particular relevance for future research on normal cognitive functioning in the healthy population, as well as for the study of cognitive impairment and clinical manifestations associated with various neuropsychiatric conditions such as schizophrenia.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Clinical utility of intraoperative arterial spin labeling for resection control in brain tumor surgery at 3 T.

Resection control in brain tumor surgery can be achieved in real time with intraoperative MRI (iMRI). Arterial spin labeling (ASL), a technique that measures cerebral blood flow (CBF) non-invasively without the use of intravenous contrast agents, can be performed intraoperatively, providing morpho-physiological information. This study aimed to evaluate the feasibility, image quality and potential to depict residual tumor of a pseudo-continuous ASL (PCASL) sequence at 3 T. Seventeen patients with brain tumors, primary (16) or metastatic (1), undergoing resection surgery with iMRI monitoring, were prospectively recruited (nine men, age 56 ± 16.6 years). A PCASL sequence with long labeling duration (3000 ms) and postlabeling delay (2000 ms) was added to the conventional protocol, which consisted of pre- and postcontrast 3D T1 -weighted (T1w) images, optional 3D-FLAIR, and diffusion. Three observers independently assessed the image quality (four-point scale) of PCASL-derived CBF maps. In those with diagnostic quality (Scores 2-4) they evaluated the presence of residual tumor using the conventional sequences first, and the CBF maps afterwards (three-point scale). Inter-observer agreement for image quality and the presence of residual tumor was assessed using Fleiss kappa statistics. The intraoperative CBF ratio of the surgical margins (i.e., perilesional CBF values normalized to contralateral gray matter CBF) was compared with preoperative CBF ratio within the tumor (Wilcoxon's test). Diagnostic ASL image quality was observed in 94.1% of patients (interobserver Fleiss κ = 0.76). PCASL showed additional foci suggestive of high-grade residual component in three patients, and a hyperperfused area extending outside the enhancing component in one patient. Interobserver agreement was almost perfect in the evaluation of residual tumor with the conventional sequences (Fleiss κ = 0.92) and substantial for PCASL (Fleiss κ = 0.80). No significant differences were found between pre and intraoperative CBF ratios (p = 0.578) in patients with residual tumor (n = 7). iMRI-PCASL perfusion is feasible at 3 T and is useful for the intraoperative assessment of residual tumor, providing in some cases additional information to the conventional sequences.

Predicting Conversion from Subjective Cognitive Decline to Mild Cognitive Impairment and Alzheimer's Disease Dementia Using Ensemble Machine Learning.

BACKGROUND: Subjective cognitive decline (SCD) may represent a preclinical stage of Alzheimer's disease (AD). Predicting progression of SCD patients is of great importance in AD-related research but remains a challenge. OBJECTIVE: To develop and implement an ensemble machine learning (ML) algorithm to identify SCD subjects at risk of conversion to mild cognitive impairment (MCI) or AD. METHODS: Ninety-nine SCD patients were included. Thirty-two progressed to MCI/AD, while 67 remained stable. To minimize the effect of class imbalance, both classes were balanced, and sensitivity was taken as evaluation metric. Bagging and boosting ML models were developed by using socio-demographic and clinical information, Mini-Mental State Examination and Geriatric Depression Scale (GDS) scores (feature-set 1a); socio-demographic characteristics and neuropsychological tests scores (feature-set 1b) and regional magnetic resonance imaging grey matter volumes (feature-set 2). The most relevant variables were combined to find the best model. RESULTS: Good prediction performances were obtained with feature-sets 1a and 2. The most relevant variables (variable importance exceeding 20%) were: Age, GDS, and grey matter volumes measured in four cortical regions of interests. Their combination provided the optimal classification performance (highest sensitivity and specificity) ensemble ML model, Extreme Gradient Boosting with over-sampling of the minority class, with performance metrics: sensitivity = 1.00, specificity = 0.92 and area-under-the-curve = 0.96. The median values based on fifty random train/test splits were sensitivity = 0.83 (interquartile range (IQR) = 0.17), specificity = 0.77 (IQR = 0.23) and area-under-the-curve = 0.75 (IQR = 0.11). CONCLUSION: A high-performance algorithm that could be translatable into practice was able to predict SCD conversion to MCI/AD by using only six predictive variables.

Update on state-of-the-art for arterial spin labeling (ASL) human perfusion imaging outside of the brain.

This review article provides an overview of developments for arterial spin labeling (ASL) perfusion imaging in the body (i.e., outside of the brain). It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. In this review, we focus on specific challenges and developments tailored for ASL in a variety of body locations. After presenting common challenges, organ-specific reviews of challenges and developments are presented, including kidneys, lungs, heart (myocardium), placenta, eye (retina), liver, pancreas, and muscle, which are regions that have seen the most developments outside of the brain. Summaries and recommendations of acquisition parameters (when appropriate) are provided for each organ. We then explore the possibilities for wider adoption of body ASL based on large standardization efforts, as well as the potential opportunities based on recent advances in high/low-field systems and machine-learning. This review seeks to provide an overview of the current state-of-the-art of ASL for applications in the body, highlighting ongoing challenges and solutions that aim to enable more widespread use of the technique in clinical practice.

Assessment of Splenic Switch-Off With Arterial Spin Labeling in Adenosine Perfusion Cardiac MRI.

BACKGROUND: In patients with suspected coronary artery disease (CAD), myocardial perfusion is assessed under rest and pharmacological stress to identify ischemia. Splenic switch-off, defined as the stress to rest splenic perfusion attenuation in response to adenosine, has been proposed as an indicator of stress adequacy. Its occurrence has been previously assessed in first-pass perfusion images, but the use of noncontrast techniques would be highly beneficial. PURPOSE: To explore the ability of pseudo-continuous arterial spin labeling (PCASL) to identify splenic switch-off in patients with suspected CAD. STUDY TYPE: Prospective. POPULATION: Five healthy volunteers (age 24.8 ± 3.8 years) and 32 patients (age 66.4 ± 8.2 years) with suspected CAD. FIELD STRENGTH/SEQUENCE: A 1.5-T/PCASL (spin-echo) and first-pass imaging (gradient-echo). ASSESSMENT: In healthy subjects, multi-delay PCASL data (500-2000 msec) were acquired to quantify splenic blood flow (SBF) and determine the adequate postlabeling delay (PLD) for single-delay acquisitions (PLD > arterial transit time). In patients, single-delay PCASL (1200 msec) and first-pass perfusion images were acquired under rest and adenosine conditions. PCASL data were used to compute SBF maps and SBF stress-to-rest ratios. Three observers classified patients into "switch-off" and "failed switch-off" groups by visually comparing rest-stress perfusion data acquired with PCASL and first-pass, independently. First-pass categories were used as reference to evaluate the accuracy of quantitative classification. STATISTICAL TESTS: Wilcoxon signed-rank, Pearson correlation, kappa, percentage agreement, Generalized Linear Mixed Model, Mann-Whitney, Pearson Chi-squared, receiver operating characteristic, area-under-the-curve (AUC) and confusion matrix. SIGNIFICANCE: P value < 0.05. RESULTS: A total of 27 patients (84.4%) experienced splenic switch-off according to first-pass categories. Comparison of PCASL-derived SBF maps during stress and rest allowed assessment of splenic switch-off, reflected in a reduction of SBF values during stress. SBF stress-to-rest ratios showed a 97% accuracy (sensitivity = 80%, specificity = 100%, AUC = 85.2%). DATA CONCLUSION: This study could demonstrate the feasibility of PCASL to identify splenic switch-off during adenosine perfusion MRI, both by qualitative and quantitative assessments. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: 2.

Gastric-phenotype Mucinous Carcinoma of the Fallopian Tube with Secondary Ovarian Involvement in a Woman with Peutz-Jeghers Syndrome: A Case Report.

Peutz-Jeghers syndrome is an autosomal dominant condition characterized by the association of hamartomatous polyps in the digestive tract, mucocutaneous pigmentation, family history, and infrequently tumors of the female genital tract with one of the most characteristic being the gastric-type endocervical adenocarcinoma. We present the case of a 75-year-old woman with a history of gastrointestinal polyps and cancer of the pancreas and breast, diagnosed with Peutz-Jeghers syndrome, who clinically debuted with a primary adnexal tumor. However, on histologic examination it was found to be a gastric-phenotype primary mucinous carcinoma tubal in origin, associated to tubal mucinous metaplasia and secondary ovarian involvement. One of her daughters had a confirmed genetic diagnosis of Peutz-Jeghers syndrome and presented with mucinous metaplasia of the tubal mucosa in the pathological study of a prophylactic hysterectomy specimen. Another of her daughters died from an ovarian juvenile granulosa cell tumor, she did not have a genetic diagnosis of Peutz-Jeghers syndrome. This case intends to highlight the rarity of gastrointestinal-type mucinous carcinomas of the ovary and fallopian tube (similar to gastric-type endocervical adenocarcinoma) in Peutz-Jeghers syndrome and emphasize the importance of genetic counseling of these patients as well as the adequate sampling of surgical specimens for early detection and treatment.

Multiparametric renal magnetic resonance imaging: A reproducibility study in renal allografts with stable function.

Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f ), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f , and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques.

Association between Circulating Levels of 25-Hydroxyvitamin D3 and Matrix Metalloproteinase-10 (MMP-10) in Patients with Type 2 Diabetes.

Background: Matrix metalloproteinase-10 (MMP-10) levels increase progressively starting from early diabetic kidney disease (DKD) stages. Vitamin D3 (vitD3) deficit is associated with a higher risk of diabetic microangiopathy. Reduced MMP-10 expression has been observed after exposure to vitD3. Aim: to assess how vitD3 status is related to MMP-10 levels in patients with Type 2 diabetes (T2D). Methods: 256 patients with T2D were included in this cross-sectional study. Demographic, clinical and serum MMP-10 and 25-hydroxyvitamin D3 (25(OH)D3) levels were collected from each patient. The association between MMP-10 and (25(OH)D3) levels was assessed using a correlation analysis and fitting a multivariate linear regression model. Results: Serum MMP-10 levels were inversely correlated with circulating 25(OH)D3 (rho = −0.25; p < 0.001). In the subgroup analysis this correlation was significant in patients with DKD (rho = −0.28; p = 0.001) and in subjects with vitD3 deficit (rho = −0.24; p = 0.005). In the regression model adjusted for kidney function, body adiposity, smoking and vitD supplementation MMP-10 levels were 68.7 pg/mL lower in patients with 25(OH)D3 > 20 ng/mL, with respect to ≤20 ng/mL (p = 0.006). Conclusions: vitD3 repletion status is an independent predictor of MMP-10 levels in T2D patients. Perhaps, high 25(OH)D3 values should be targeted in these patients in order to prevent vascular complications.

Recent Technical Developments in ASL: A Review of the State of the Art.

This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.