Unilateral Magnetic Resonance-Guided Focused Ultrasound Lesion of the Subthalamic Nucleus in Parkinson's Disease: A Prospective Study.

BACKGROUND: Unilateral subthalamic nucleus (STN) ablation using magnetic resonance-guided focused ultrasound (MRgFUS) is being explored as a new treatment for asymmetric Parkinson's disease (PD). OBJECTIVES: The aims were to study the efficacy and safety of this treatment in asymmetric PD patients and to characterize the lesions. METHODS: This prospective, single-center, open-label study evaluated asymmetric PD patients at 6 (n = 20) and 12 months (n = 12) after MRgFUS lesion of the STN. The primary outcome was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), score in off medication on the treated side and the adverse events (AEs) at 6-month follow-up. We also evaluated cognitive-neuropsychological changes, self-assessment of clinical improvement, and the correlation of the lesion volume with the motor outcomes. RESULTS: On the treated side, the MDS-UPDRS III score (mean difference = 13.8) and the scores in rigidity, bradykinesia, and tremor improved (P < 0.001) throughout the follow-up compared to baseline (at 6 months: rigidity mean difference = 2.8, improvement: 83.5%; bradykinesia mean difference = 6.0, improvement: 69.4%; tremor mean difference = 4.7, improvement: 91.5%). One patient had severe weakness in the treated hemibody, 1 had moderate dyskinesia, and 1 was in moderate confusional state that became mild (weakness) or completely resolved (dyskinesia and confusional state) at 6 months. The rest of the AEs were mild. We observed no clinically relevant changes in cognitive-neuropsychological tests. The percentage of ablation of the STN correlated with the improvement in the total MDS-UPDRS III and contralateral tremor scores (P < 0.05). CONCLUSION: Unilateral MRgFUS lesion of the STN resulted in a significant motor improvement. We observed no persistent severe AEs, although mild, mostly transient AEs were frequent. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

3-T MR-guided focused ultrasound thalamotomy for tremor in patients with a cardiac pacemaker: case series and review of the literature.

MR-guided focused ultrasound (MRgFUS) has proven its efficacy and safety for the treatment of essential tremor (ET) and/or Parkinson's disease (PD). However, having a cardiac pacemaker has been considered an exclusion criterion for the use of MRgFUS. Only 2 patients with a cardiac pacemaker treated with MRgFUS have been previously reported, both treated using 1.5-T MRI. In this paper, the authors present their experience performing 3-T MRgFUS thalamotomy in 4 patients with an implanted cardiac pacemaker. Treatments were uneventful regarding complications or severe side effects. MRgFUS using 3-T MRI was found to be an efficient and safe treatment for ET and/or PD in patients with an MRI-compatible pacemaker.

Functional impact of subthalamotomy by magnetic resonance-guided focused ultrasound in Parkinson's disease: a hybrid PET/MR study of resting-state brain metabolism.

PURPOSE: Subthalamotomy using magnetic resonance-guided focused ultrasound (MRgFUS) has become a potential treatment option for the cardinal features of Parkinson's disease (PD). The purpose of this study was to evaluate the effects of MRgFUS-subthalamotomy on brain metabolism using different scale levels. METHODS: We studied resting-state glucose metabolism in eight PD patients before and after unilateral MRgFUS-subthalamotomy using hybrid [18F]FDG-PET/MR imaging. We used statistical nonparametric mapping (SnPM) to study regional metabolic changes following this treatment and also quantified whole-brain treatment-related changes in the expression of a spatial covariance-based Parkinson's disease-related metabolic brain pattern (PDRP). Modulation of regional and network activity was correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor scores. RESULTS: After subthalamotomy, there was a significant reduction in FDG uptake in the subthalamic region, globus pallidus internus, motor and premotor cortical regions, and cingulate gyrus in the treated hemisphere, and the contralateral cerebellum (p < 0.001). Diffuse metabolic increase was found in the posterior parietal and occipital areas. Treatment also resulted in a significant decline in PDRP expression (p < 0.05), which correlated with clinical improvement in UPDRS motor scores (rho = 0.760; p = 0.002). CONCLUSIONS: MRgFUS-subthalamotomy induced metabolic alterations in distributed nodes of the motor, associative, and limbic circuits. Clinical improvement was associated with reduction in the PDRP expression. This treatment-induced modulation of the metabolic network is likely to mediate the clinical benefit achieved following MRgFUS-subthalamotomy.

Machine learning in the integration of simple variables for identifying patients with myocardial ischemia.

BACKGROUND: A significant number of variables are obtained when characterizing patients suspected with myocardial ischemia or at risk of MACE. Guidelines typically use a handful of them to support further workup or therapeutic decisions. However, it is likely that the numerous available predictors maintain intrinsic complex interrelations. Machine learning (ML) offers the possibility to elucidate complex patterns within data to optimize individual patient classification. We evaluated the feasibility and performance of ML in utilizing simple accessible clinical and functional variables for the identification of patients with ischemia or an elevated risk of MACE as determined through quantitative PET myocardial perfusion reserve (MPR). METHODS: 1,234 patients referred to Nitrogen-13 ammonia PET were analyzed. Demographic (4), clinical (8), and functional variables (9) were retrieved and input into a cross-validated ML workflow consisting of feature selection and modeling. Two PET-defined outcome variables were operationalized: (1) any myocardial ischemia (regional MPR < 2.0) and (2) an elevated risk of MACE (global MPR < 2.0). ROC curves were used to evaluate ML performance. RESULTS: 16 features were included for boosted ensemble ML. ML achieved an AUC of 0.72 and 0.71 in identifying patients with myocardial ischemia and with an elevated risk of MACE, respectively. ML performance was superior to logistic regression when the latter used the ESC guidelines risk models variables for both PET-defined labels (P < .001 and P = .01, respectively). CONCLUSIONS: ML is feasible and applicable in the evaluation and utilization of simple and accessible predictors for the identification of patients who will present myocardial ischemia and an elevated risk of MACE in quantitative PET imaging.

Topography of Cholinergic Changes in Dementia With Lewy Bodies and Key Neural Network Hubs.

OBJECTIVES: The authors investigated the topography of cholinergic vulnerability in patients with dementia with Lewy bodies (DLB) using positron emission tomography (PET) imaging with the vesicular acetylcholine transporter (VAChT) [18F]-fluoroethoxybenzovesamicol ([18F]-FEOBV) radioligand. METHODS: Five elderly participants with DLB (mean age, 77.8 years [SD=4.2]) and 21 elderly healthy control subjects (mean age, 73.62 years [SD=8.37]) underwent clinical assessment and [18F]-FEOBV PET. RESULTS: Compared with the healthy control group, reduced VAChT binding in patients with DLB demonstrated nondiffuse regionally distinct and prominent reductions in bilateral opercula and anterior cingulate to mid-cingulate cortices, bilateral insula, right (more than left) lateral geniculate nuclei, pulvinar, right proximal optic radiation, bilateral anterior and superior thalami, and posterior hippocampal fimbria and fornices. CONCLUSIONS: The topography of cholinergic vulnerability in DLB comprises key neural hubs involved in tonic alertness (cingulo-opercular), saliency (insula), visual attention (visual thalamus), and spatial navigation (fimbria/fornix) networks. The distinct denervation pattern suggests an important cholinergic role in specific clinical disease-defining features, such as cognitive fluctuations, visuoperceptual abnormalities causing visual hallucinations, visuospatial changes, and loss of balance caused by DLB.

A Novel Noninvasive Approach Based on SPECT and EEG for the Location of the Epileptogenic Zone in Pharmacoresistant Non-Lesional Epilepsy.

Background and objectives: The aim of this study is to propose a methodology that combines non-invasive functional modalities electroencephalography (EEG) and single photon emission computed tomography (SPECT) to estimate the location of the epileptogenic zone (EZ) for the presurgical evaluation of patients with drug-resistant non-lesional epilepsy. Materials and Methods: This methodology consists of: (i) Estimation of ictal EEG source imaging (ESI); (ii) application of the subtraction of ictal and interictal SPECT co-registered with MRI (SISCOM) methodology; and (iii) estimation of ESI but using the output of the SISCOM as a priori information for the estimation of the sources. The methodology was implemented in a case series as an example of the application of this novel approach for the presurgical evaluation. A gold standard and a coincidence analysis based on measures of sensitivity and specificity were used as a preliminary assessment of the proposed methodology to localize EZ. Results: In patients with good postoperative evolution, the estimated EZ presented a spatial coincidence with the resection site represented by high values of sensitivity and specificity. For the patient with poor postoperative evolution, the methodology showed a partial incoherence between the estimated EZ and the resection site. In cases of multifocal epilepsy, the method proposed spatially extensive epileptogenic zones. Conclusions: The results of the case series provide preliminary evidence of the methodology's potential to epileptogenic zone localization in non-lesion drug-resistant epilepsy. The novelty of the article consists in estimating the sources of ictal EEG using SISCOM result as a prior for the inverse solution. Future studies are necessary in order to validate the described methodology. The results constitute a starting point for further studies in order to support the clinical reliability of the proposed methodology and advocate for their implementation in the presurgical evaluation of patients with intractable non-lesional epilepsy.

The number of optic neuritis attacks is a potential confounder when comparing patients with NMO vs. controls by voxel-based neuroimaging analysis.

BACKGROUND: Voxel-based morphometric (VBM) studies in neuromyelitis optica (NMO) have shown limited reproducibility. A previous study suggests that the number of optic neuritis (ON) attacks may be a confounding factor when comparing NMO patients with controls if it is not taken into account during VBM analysis. PURPOSE: To investigate the potential confounding effect of the number of ON attacks, for both tissue volumes and perfusion by voxel-based statistical analysis. MATERIAL AND METHODS: Volumetric magnetic resonance imaging (MRI) and perfusion SPECT were obtained from 15 controls and two patient subgroups: subgroup I was composed of nine patients with one or two ON attacks; and subgroup II of six patients with three or four ON attacks. We performed non-parametric voxel-based comparison of tissue volumes and perfusion between controls versus the two patient subgroups and for the whole patient group. RESULTS: Subgroup I presented no volume reductions, contrary to subgroup II that showed unequivocal reduction. We also found hypoperfusion in different brain regions in different subgroups. The results were quite different for the whole patient group. CONCLUSION: These findings highlight the confounding effect of the number of ON attacks, providing a new methodological insight that could explain the limited reproducibility of previous VBM studies in NMO.

Studying the topological organization of the cerebral blood flow fluctuations in resting state.

In this paper the cerebral blood flow (CBF) in resting state obtained from SPECT imaging is employed as a hemodynamics descriptor to study the concurrent changes between brain structures and to build binarized connectivity graphs. The statistical similarity in CBF between pairs of regions was measured by computing the Pearson correlation coefficient across 31 normal subjects. We demonstrated the CBF connectivity matrices follow 'small-world' attributes similar to previous studies using different modalities of neuroimaging data (MRI, fMRI, EEG, MEG). The highest concurrent fluctuations in CBF were detected between homologous cortical regions (homologous callosal connections). It was found that the existence of structural core regions or hubs positioned on a high proportion of shortest paths within the CBF network. These were anatomically distributed in frontal, limbic, occipital and parietal regions that suggest its important role in functional integration. Our findings point to a new possibility of using CBF variable to investigate the brain networks based on graph theory in normal and pathological states. Likewise, it opens a window to future studies to link covariation between morphometric descriptors, axonal connectivity and CBF processes with a potential diagnosis applications.

Deep learning in neuroimaging of epilepsy.

In recent years, artificial intelligence, particularly deep learning (DL), has demonstrated utility in diverse areas of medicine. DL uses neural networks to automatically learn features from the raw data while this is not possible with conventional machine learning. It is helpful for the assessment of patients with epilepsy and whilst most published studies have been aimed at the automatic detection and prediction of seizures from electroencephalographic records, there is a growing number of investigations that use neuroimaging modalities (structural and functional magnetic resonance imaging, diffusion-weighted imaging and positron emission tomography) as input data. We review the application of DL to neuroimaging (sMRI, fMRI, DWI and PET) of focal epilepsy, specifically presurgical evaluation of drug-refractory epilepsy. First, a brief theoretical overview of artificial neural networks and deep learning is presented. Next, we review applications of deep learning to neuroimaging of epilepsy: diagnosis and lateralization, automated detection of lesion, presurgical evaluation and prediction of postsurgical outcome. Finally, the limitations, challenges and possible future directions in the application of these methods in the study of epilepsies are discussed. This approach could become an essential tool in clinical practice, particularly in the evaluation of images considered negative by visual inspection, in individualized treatments, and in the approach to epilepsy as a network disorder. However, greater multicenter collaboration is required to achieve the collection of sufficient data with the required quality together with the open access availability of the developed codes and tools.

Striatal Acetylcholine-Dopamine Imbalance in Parkinson Disease: In Vivo Neuroimaging Study with Dual-Tracer PET and Dopaminergic PET-Informed Correlational Tractography.

Previous studies of animal models of Parkinson disease (PD) suggest an imbalance between striatal acetylcholine and dopamine, although other studies have questioned this. To our knowledge, there are no previous in vivo neuroimaging studies examining striatal acetylcholine-dopamine imbalance in PD patients. Using cholinergic and dopaminergic PET (18F-fluoroethoxybenzovesamicol [18F-FEOBV] and 11C-dihydrotetrabenazine [11C-DTBZ], respectively) and correlational tractography, our aim was to investigate the acetylcholine-dopamine interaction at 2 levels of dopaminergic loss in PD subjects: integrity loss of the nigrostriatal dopaminergic white matter tract and loss at the presynaptic-terminal level. Methods: The study involved 45 subjects with mild to moderate PD (36 men, 9 women; mean age, 66.3 ± 6.3 y, disease duration, 5.8 ± 3.6 y; Hoehn and Yahr stage, 2.2 ± 0.6) and 15 control subjects (9 men, 6 women; mean age, 69.1 ± 8.6 y). PET imaging was performed using standard protocols. We first estimated the integrity of the dopaminergic nigrostriatal white matter tracts in PD subjects by incorporating molecular information from striatal 11C-DTBZ PET into the fiber tracking process using correlational tractography (based on quantitative anisotropy [QA], a measure of tract integrity). Subsequently, we used voxel-based correlation to test the association of the mean QA of the nigrostriatal tract of each cerebral hemisphere with the striatal 18F-FEOBV distribution volume ratio (DVR) in PD subjects. The same analysis was performed for 11C-DTBZ DVR in 12 striatal subregions (presynaptic-terminal level). Results: Unlike 11C-DTBZ DVR in striatal subregions, the mean QA of the nigrostriatal tract of the most affected hemisphere showed a negative correlation with a striatal cluster of 18F-FEOBV DVR in PD subjects (corrected P = 0.039). We also found that the mean 18F-FEOBV DVR within this cluster was higher in the PD group than in the control group (P = 0.01). Cross-validation analyses confirmed these findings. We also found an increase in bradykinesia ratings associated with increased acetylcholine-dopamine imbalance in the most affected hemisphere (r = 0.41, P = 0.006). Conclusion: Our results provide evidence for the existence of striatal acetylcholine-dopamine imbalance in early PD and may provide an avenue for testing in vivo effects of therapeutic strategies aimed at restoring striatal acetylcholine-dopamine balance in PD.

Cerebral topography of vesicular cholinergic transporter changes in neurologically intact adults: A [18F]FEOBV PET study.

Acetylcholine plays a major role in brain cognitive and motor functions with regional cholinergic terminal loss common in several neurodegenerative disorders. We describe age-related declines of regional cholinergic neuron terminal density in vivo using the positron emission tomography (PET) ligand [18F](-)5-Fluoroethoxybenzovesamicol ([18F] FEOBV), a vesamicol analogue selectively binding to the vesicular acetylcholine transporter (VAChT). A total of 42 subjects without clinical evidence of neurologic disease (mean 50.55 [range 20-80] years, 24 Male/18 Female) underwent [18F]FEOBV brain PET imaging. We used SPM based voxel-wise statistical analysis to perform whole brain voxel-based parametric analysis (family-wise error corrected, FWE) and to also extract the most significant clusters of regions correlating with aging with gender as nuisance variable. Age-related VAChT binding reductions were found in primary sensorimotor cortex, visual cortex, caudate nucleus, anterior to mid-cingulum, bilateral insula, para-hippocampus, hippocampus, anterior temporal lobes/amygdala, dorsomedial thalamus, metathalamus, and cerebellum (gender and FWE-corrected, P < 0.05). These findings show a specific topographic pattern of regional vulnerability of cholinergic nerve terminals across multiple cholinergic systems accompanying aging.

Effects of interventions on cerebral perfusion in the Alzheimer's disease spectrum: A systematic review.

Cerebral perfusion dysfunctions are seen in the early stages of Alzheimer's disease (AD). We systematically reviewed the literature to investigate the effect of pharmacological and non-pharmacological interventions on cerebral hemodynamics in randomized controlled trials involving AD patients or Mild Cognitive Impairment (MCI) due to AD. Studies involving other dementia types were excluded. Data was searched in April 2021 on MEDLINE, Embase, and Web of Science. Risk of bias was assessed using Cochrane Risk of Bias Tool. A meta-synthesis was performed separating results from MCI and AD studies. 31 studies were included and involved 310 MCI and 792 CE patients. The MCI studies (n = 8) included physical, cognitive, dietary, and pharmacological interventions. The AD studies (n = 23) included pharmacological, physical interventions, and phytotherapy. Cerebral perfusion was assessed with PET, ASL, Doppler, fNIRS, DSC-MRI, Xe-CT, and SPECT. Randomization and allocation concealment methods and subject characteristics such as AD-onset, education, and ethnicity were missing in several papers. Positive effects on hemodynamics were seen in 75 % of the MCI studies, and 52 % of the AD studies. Inserting cerebral perfusion outcome measures, together with established AD biomarkers, is fundamental to target all disease mechanisms and understand the role of cerebral perfusion in AD.

The effect of lesion filling on brain network analysis in multiple sclerosis using structural magnetic resonance imaging.

BACKGROUND: Graph theoretical network analysis with structural magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients can be used to assess subtle changes in brain networks. However, the presence of multiple focal brain lesions might impair the accuracy of automatic tissue segmentation methods, and hamper the performance of graph theoretical network analysis. Applying "lesion filling" by substituting the voxel intensities of a lesion with the voxel intensities of nearby voxels, thus creating an image devoid of lesions, might improve segmentation and graph theoretical network analysis. This study aims to determine if brain networks are different between MS subtypes and healthy controls (HC) and if the assessment of these differences is affected by lesion filling. METHODS: The study included 49 MS patients and 19 HC that underwent a T1w, and T2w-FLAIR MRI scan. Graph theoretical network analysis was performed from grey matter fractions extracted from the original T1w-images and T1w-images after lesion filling. RESULTS: Artefacts in lesion-filled T1w images correlated positively with total lesion volume (r = 0.84, p < 0.001) and had a major impact on grey matter segmentation accuracy. Differences in sensitivity for network alterations were observed between original T1w data and after application of lesion filling: graph theoretical network analysis obtained from lesion-filled T1w images produced more differences in network organization in MS patients. CONCLUSION: Lesion filling might reduce variability across subjects resulting in an increased detection rate of network alterations in MS, but also induces significant artefacts, and therefore should be applied cautiously especially in individuals with higher lesions loads.

Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease: In Vivo Neuroimaging Study of 11C-DTBZ PET Combined with Correlational Tractography.

Previous histopathologic and animal studies have shown axonal impairment and loss of connectivity of the nigrostriatal pathway in Parkinson disease (PD). However, there are conflicting reports from in vivo human studies. 11C-dihydrotetrabenazine (11C-DTBZ) is a vesicular monoamine type 2 transporter PET ligand that allows assessment of nigrostriatal presynaptic dopaminergic terminal integrity. Correlational tractography based on diffusion MRI can incorporate ligand-specific information provided by 11C-DTBZ PET into the fiber-tracking process. The purpose of this study was to assess the in vivo association between the integrity of the nigrostriatal tract (defined by correlational tractography) and the degree of striatal dopaminergic denervation based on 11C-DTBZ PET. Methods: The study involved 30 subjects with mild to moderate PD (23 men and 7 women; mean age, 66 ± 6.2 y; disease duration, 6.4 ± 4.0 y; Hoehn and Yahr stage, 2.1 ± 0.6; Movement Disorder Society [MDS]-revised Unified Parkinson Disease Rating Scale [UPDRS] [I-III] total score, 43.4 ± 17.8) and 30 control subjects (18 men and 12 women; mean age, 62 ± 10.3 y). 11C-DTBZ PET was performed using standard synthesis and acquisition protocols. Correlational tractography was performed to assess quantitative anisotropy (QA; a measure of tract integrity) of white matter fibers correlating with information derived from striatal 11C-DTBZ data using the DSI Studio toolbox. Scans were realigned according to least and most clinically affected cerebral hemispheres. Results: Nigrostriatal tracts were identified in both hemispheres of PD patients. Higher mean QA values along the identified tracts were significantly associated with higher striatal 11C-DTBZ distribution volume ratios (least affected: r = 0.57, P = 0.001; most affected: r = 0.44, P = 0.02). Lower mean QA values of the identified tract in the LA hemisphere associated with increased severity of bradykinesia sub-score derived from MDS-UPDRS part III (r = -0.42; P = 0.02). Cross-validation revealed the generalizability of these results. Conclusion: These findings suggest that impaired integrity of dopaminergic nigrostriatal nerve terminals is associated with nigrostriatal axonal dysfunction in mild to moderate PD. Assessment of nigrostriatal tract integrity may be suitable as a biomarker of early- or even prodromal-stage PD.

Regional cerebral cholinergic nerve terminal integrity and cardinal motor features in Parkinson's disease.

Clinical effects of anti-cholinergic drugs implicate cholinergic systems alterations in the pathophysiology of some cardinal motor impairments in Parkinson's disease. The topography of affected cholinergic systems deficits and motor domain specificity are poorly understood. Parkinson's disease patients (n = 108) underwent clinical and motor assessment and vesicular acetylcholine transporter [18F]-fluoroethoxybenzovesamicol PET imaging. Volumes-of-interest-based analyses included detailed thalamic and cerebellar parcellations. Successful PET sampling for most of the small-sized parcellations was available in 88 patients. A data-driven approach, stepwise regression using the forward selection method, was used to identify cholinergic brain regions associating with cardinal domain-specific motor ratings. Regressions with motor domain scores for model-selected regions followed by confounder analysis for effects of age of onset, duration of motor disease and levodopa equivalent dose were performed. Among 7 model-derived regions associating with postural instability and gait difficulties domain scores three retained significance in confounder variable analysis: medial geniculate nucleus (standardized ß = -0.34, t = -3.78, P = 0.0003), lateral geniculate nucleus (ß = -0.32, t = -3.4, P = 0.001) and entorhinal cortex (ß = -0.23, t = -2.6, P = 0.011). A sub-analysis of non-episodic postural instability and gait difficulties scores demonstrated significant effects of the medial geniculate nucleus, entorhinal cortex and globus pallidus pars interna. Among 6 tremor domain model-selected regions two regions retained significance in confounder variable analysis: cerebellar vermis section of lobule VIIIb (ß = -0.22, t = -2.4, P = 0.021) and the putamen (ß = -0.23, t = -2.3, P = 0.024). None of the three model-selected variables for the rigidity domain survived confounder analysis. Two out of the four model-selected regions for the distal limb bradykinesia domain survived confounder analysis: globus pallidus pars externa (ß = 0.36, t = 3.9, P = 0.0097) and the paracentral lobule (ß = 0.26, t = 2.5, P = 0.013). Emphasizing the utility of a systems-network conception of the pathophysiology of Parkinson's disease cardinal motor features, our results are consistent with specific deficits in basal forebrain corticopetal, peduncupontine-laterodorsal tegmental complex, and medial vestibular nucleus cholinergic pathways, against the background of nigrostriatal dopaminergic deficits, contributing significantly to postural instability, gait difficulties, tremor and distal limb bradykinesia cardinal motor features of Parkinson's disease. Our results suggest significant and distinct consequences of degeneration of cholinergic peduncupontine-laterodorsal tegmental complex afferents to both segments of the globus pallidus. Non-specific regional cholinergic nerve terminal associations with rigidity scores likely reflect more complex multifactorial signalling mechanisms with smaller contributions from cholinergic pathways.

Brain anatomy, cerebral blood flow, and connectivity in the transition from PVS to MCS.

BACKGROUND: We report a 15 year-old girl with sickle cell disease, who developed important cognitive impairment due to multiple strokes, and who had been diagnosed with PVS. Nonetheless, when she was later admitted to our Institute, according to the presence of inconsistent but clearly demonstrable behavioral evidence of consciousness awareness, we changed our diagnosis to MCS. METHODS: This patient was studied by T1 MRI images, co-registration of fractional anisotropy (FA), and SPECT with MRI. RESULTS: Brain structures were mainly preserved in posterior areas of both cerebral hemispheres, although small tissue islands were present in both frontal lobes, mainly preserved in the right one. SPECT showed CBF preservation in posterior brain regions and in the cerebellum, and in those frontal small islands of tissue lateralized to the right frontal lobe; meanwhile FA showed preservation of anatomical connectivity among posterior and frontal brain regions. These remaining cortical regions are also connected with the thalami. CONCLUSION: These results showing connectivity among posterior and frontal cortical and probably with other subcortical regions, and CBF preservation in these areas, might explain the recovery of minimum awareness despite huge anatomical brain lesions.

Autologous bone marrow stem cell neurotransplantation in stroke patients. An open study.

PURPOSE: Bone marrow stem cells (BMSC) were transplanted into the perilesional area in five patients bearing sequels of stroke, to evaluate the safety of the procedure and tolerance to the transplanted cells. METHODS: Cells were obtained from bone marrow samples taken from the same patient and stereotactically implanted into the targets, determined using a combination of images, and trans-operative recording of multiunit activity. The cells were implanted in several points along tracts in the perilesional region. RESULTS: No important adverse events derived from surgery or transplant were observed during the one year follow-up period, or detected using a combination of tests and functional measurements applied pre- and post-surgically. In contrast, some improvements were observed regarding the neurological condition of the patients, but the small number of patients in the study does not allow any conclusive statement. CONCLUSIONS: Our results demonstrate that BMSC can be safely transplanted into the brain of patients, with excellent tolerance and without complications, using the methods described here.

Episodic memory in mild cognitive impairment inversely correlates with the global modularity of the cerebral blood flow network.

Cerebral blood flow (CBF) SPECT is an interesting methodology to study brain connectivity in mild cognitive impairment (MCI) since it is accessible worldwide and can be used as a biomarker of neuronal injury in MCI. In CBF SPECT, connectivity is grounded in group-based correlation networks. Therefore, topological metrics derived from the CBF correlation network cannot be used to support diagnosis and prognosis individually. However, methods to extract the individual patient contribution to topological metrics of group-based correlation networks were developed although not yet applied to MCI patients. Here, we investigate whether the episodic memory of 24 amnestic MCI patients correlates with individual patient contributions to topological metrics of the CBF correlation network. We first compared topological metrics of the MCI group network with the network corresponding to 26 controls. Metrics that showed significant differences were then used for the individual patient contribution analysis. We found that the global network modularity was increased while global efficiency decreased in the MCI network compared to the control. Most importantly, we found that episodic memory inversely correlates with the patient contribution to the global network modularity, which highlights the potential of this approach to develop a CBF connectivity-based biomarker at the individual level.

FDG-PET for Prediction of AD Dementia in Mild Cognitive Impairment. A Review of the State of the Art with Particular Emphasis on the Comparison with Other Neuroimaging Modalities (MRI and Perfusion SPECT).

This review article aims at providing a state-of-the-art review of the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging (FDG-PET) in the prediction of Alzheimer's dementia in subjects suffering mild cognitive impairment (MCI), with a particular focus on the predictive power of FDG-PET compared to structural magnetic resonance imaging (sMRI). We also address perfusion single photon emission computed tomography (SPECT) as a less costly and more accessible alternative to FDG-PET. A search in PubMed was performed, taking into consideration relevant scientific articles published in English within the last five years and limited to human studies. This recent literature confirms the effectiveness of FDG-PET and sMRI for prediction of AD dementia in MCI. However, there are discordant results regarding which image modality is superior. This could be explained by the high variability of metrics used to evaluate both imaging modalities and/or by sampling/population issues such as age, disease severity and conversion time. FDG-PET seems to outperform sMRI in rapidly converting early-onset MCI individuals, whereas sMRI may outperform FDG-PET in late-onset MCI subjects, in which case FDG PET might only provide a complementary role. Although FDG-PET performs better than perfusion SPECT, current evidence confirms perfusion SPECT as a valid alternative when FDG- PET is not available. Finally, possible future directions in the field are discussed.

Subtle alterations in cerebrovascular reactivity in mild cognitive impairment detected by graph theoretical analysis and not by the standard approach.

There is growing support that cerebrovascular reactivity (CVR) in response to a vasodilatory challenge, also defined as the cerebrovascular reserve, is reduced in Alzheimer's disease dementia. However, this is less clear in patients with mild cognitive impairment (MCI). The current standard analysis may not reflect subtle abnormalities in CVR. In this study, we aimed to investigate vasodilatory-induced changes in the topology of the cerebral blood flow correlation (CBFcorr) network to study possible network-related CVR abnormalities in MCI. For this purpose, four CBFcorr networks were constructed: two using CBF SPECT data at baseline and under the vasodilatory challenge of acetazolamide (ACZ), obtained from a group of 26 MCI patients; and two equivalent networks from a group of 26 matched cognitively normal controls. The mean strength of association (SA) and clustering coefficient (C) were used to evaluate ACZ-induced changes on the topology of CBFcorr networks. We found that cognitively normal adults and MCI patients show different patterns of C and SA changes. The observed differences included the medial prefrontal cortices and inferior parietal lobe, which represent areas involved in MCI's cognitive dysfunction. In contrast, no substantial differences were detected by standard CVR analysis. These results suggest that graph theoretical analysis of ACZ-induced changes in the topology of the CBFcorr networks allows the identification of subtle network-related CVR alterations in MCI, which couldn't be detected by the standard approach.