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.

Breath-Hold Induced Cerebrovascular Reactivity Measurements Using Optimized Pseudocontinuous Arterial Spin Labeling.

A pseudocontinuous arterial spin labeling (PCASL) sequence combined with background suppression and single-shot accelerated 3D RARE stack-of-spirals was used to evaluate cerebrovascular reactivity (CVR) induced by breath-holding (BH) in ten healthy volunteers. Four different models designed using the measured change in PETCO2 induced by BH were compared, for CVR quantification. The objective of this comparison was to understand which regressor offered a better physiological model to characterize the cerebral blood flow response under BH. The BH task started with free breathing of 42 s, followed by interleaved end-expiration BHs of 21 s, for ten cycles. The total scan time was 12 min and 20 s. The accelerated readout allowed the acquisition of PCASL data with better temporal resolution than previously used, without compromising the post-labeling delay. Elevated CBF was observed in most cerebral regions under hypercapnia, which was delayed with respect to the BH challenge. Significant statistical differences in CVR were obtained between the different models in GM (p < 0.0001), with ramp models yielding higher values than boxcar models and between the two tissues, GM and WM, with higher values in GM, in all the models (p < 0.0001). The adjustment of the ramp amplitude during each BH cycle did not improve the results compared with a ramp model with a constant amplitude equal to the mean PETCO2 change during the experiment.

Coupling of cerebral blood flow and functional connectivity is decreased in healthy aging.

Aging leads to cerebral perfusion and functional connectivity changes that have been assessed using various neuroimaging techniques. In addition, a link between these two parameters has been demonstrated in healthy young adults. In this work, we employed arterial spin labeling (ASL) fMRI to measure global and voxel-wise differences in cerebral blood flow (CBF) and intrinsic connectivity contrast (ICC) in the resting state in a group of cognitively normal elderly subjects and a group of cognitively normal young subjects, in order to assess the effects of aging on CBF-ICC coupling, which had not been previously evaluated. Our results showed age-related global and regional CBF decreases in prefrontal mesial areas, lateral frontal regions, insular cortex, lateral parietal areas, precuneus and occipital regions. Subcortically, perfusion was reduced in the medial thalamus and caudate nucleus. ICC was also found reduced with age in prefrontal cortical areas and insular cortex, affecting key nodes of the default mode and salience networks. Areas of ICC and CBF decrease partially overlapped, however, the CBF reduction was more extensive and encompassed more areas. This dissociation was accompanied by a decrease in CBF-ICC coupling. These results suggest that aging leads to a disruption in the relationship between CBF and intrinsic functional connectivity that could be due to neurovascular dysregulation.

Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience.

We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM). Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin-eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre- and postoperative volumetric magnetic resonance imaging. Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin-eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%. The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor border.