Procedural learning and retention relative to explicit learning and retention in mild cognitive impairment and Alzheimer's disease using a modification of the trail making test.

Amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) dementia are characterized by pathological changes to the medial temporal lobes, resulting in explicit learning and retention reductions. Studies demonstrate that implicit/procedural memory processes are relatively intact in these populations, supporting different anatomical substrates for differing memory systems. This study examined differences between explicit and procedural learning and retention in individuals with aMCI and AD dementia relative to matched healthy controls. We also examined anatomical substrates using volumetric MRI. Results revealed expected difficulties with explicit learning and retention in individuals with aMCI and AD with relatively preserved procedural memory. Explicit verbal retention was associated with medial temporal cortex volumes. However, procedural retention was not related to medial temporal or basal ganglia volumes. Overall, this study confirms the dissociation between explicit relative to procedural learning and retention in aMCI and AD dementia and supports differing anatomical substrates.

Frontal and temporal lobe correlates of verbal learning and memory in aMCI and suspected Alzheimer's disease dementia.

Alzheimer's disease is primarily known for deficits in learning and retaining new information. This has long been associated with pathological changes in the mesial temporal lobes. The role of the frontal lobes in memory in Alzheimer's disease is less well understood. In this study, we examined the role of the frontal lobes in learning, recognition, and retention of new verbal information, as well as the presence of specific errors (i.e., intrusions and false-positive errors). Participants included one hundred sixty-seven patients clinically diagnosed with amnestic mild cognitive impairment or suspected Alzheimer's disease dementia who were administered the California Verbal Learning Test and completed high-resolution MRI. We confirmed the role of the mesial temporal lobes in learning and retention, including the volumes of the hippocampus, entorhinal cortex, and parahippocampal gyrus. In addition, false-positive errors were associated with all volumes of the mesial temporal lobes and widespread areas within the frontal lobes. Errors of intrusion were related to the supplementary motor cortex and hippocampus. Most importantly, the mesial temporal lobes interacted with the frontal lobes for learning, recognition, and memory errors. Lower volumes in both regions explained more performance variance than any single structure. This study supports the interaction of the frontal lobes with the temporal lobes in many aspects of memory in Alzheimer's disease.

Focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: long-term safety, imaging, and cognitive outcomes.

OBJECTIVE: MRI-guided low-intensity focused ultrasound (FUS) has been shown to reversibly open the blood-brain barrier (BBB), with the potential to deliver therapeutic agents noninvasively to target brain regions in patients with Alzheimer's disease (AD) and other neurodegenerative conditions. Previously, the authors reported the short-term safety and feasibility of FUS BBB opening of the hippocampus and entorhinal cortex (EC) in patients with AD. Given the need to treat larger brain regions beyond the hippocampus and EC, brain volumes and locations treated with FUS have now expanded. To evaluate any potential adverse consequences of BBB opening on disease progression, the authors report safety, imaging, and clinical outcomes among participants with mild AD at 6-12 months after FUS treatment targeted to the hippocampus, frontal lobe, and parietal lobe. METHODS: In this open-label trial, participants with mild AD underwent MRI-guided FUS sonication to open the BBB in ß-amyloid positive regions of the hippocampus, EC, frontal lobe, and parietal lobe. Participants underwent 3 separate FUS treatment sessions performed 2 weeks apart. Outcome assessments included safety, imaging, neurological, cognitive, and florbetaben ß-amyloid PET. RESULTS: Ten participants (range 55-76 years old) completed 30 separate FUS treatments at 2 participating institutions, with 6-12 months of follow-up. All participants had immediate BBB opening after FUS and BBB closure within 24-48 hours. All FUS treatments were well tolerated, with no serious adverse events related to the procedure. All 10 participants had a minimum of 6 months of follow-up, and 7 participants had a follow-up out to 1 year. Changes in the Alzheimer's Disease Assessment Scale-cognitive and Mini-Mental State Examination scores were comparable to those in controls from the Alzheimer's Disease Neuroimaging Initiative. PET scans demonstrated an average ß-amyloid plaque of 14% in the Centiloid scale in the FUS-treated regions. CONCLUSIONS: This study is the largest cohort of participants with mild AD who received FUS treatment, and has the longest follow-up to date. Safety was demonstrated in conjunction with reversible and repeated BBB opening in multiple cortical and deep brain locations, with a concomitant reduction of ß-amyloid. There was no apparent cognitive worsening beyond expectations up to 1 year after FUS treatment, suggesting that the BBB opening treatment in multiple brain regions did not adversely influence AD progression. Further studies are needed to determine the clinical significance of these findings. FUS offers a unique opportunity to decrease amyloid plaque burden as well as the potential to deliver targeted therapeutics to multiple brain regions in patients with neurodegenerative disorders.

Effect of antenatal magnesium sulphate on MRI biomarkers of white matter development at term equivalent age: The MagNUM Study.

BACKGROUND: Magnesium sulphate given to women prior to very preterm birth protects the perinatal brain, so fewer babies die or develop cerebral palsy. How magnesium sulphate exerts these beneficial effects remains uncertain. The MagNUM Study aimed to assess the effect of exposure to antenatal magnesium sulphate on MRI measures of brain white matter microstructure at term equivalent age. METHODS: Nested cohort study within the Magnesium sulphate at 30 to <34 weeks' Gestational age Neuroprotection Trial (MAGENTA). Australian New Zealand Clinical Trials Registry ACTRN12611000491965. Mothers at risk of preterm birth at 30 to <34 weeks' gestation were randomised to receive either 4 g of magnesium sulphate heptahydrate [8 mmol magnesium ions], or saline placebo, when preterm birth was planned or expected within 24 h. Participating babies underwent diffusion tensor MRI at term equivalent age. The main outcomes were fractional anisotropy across the white matter tract skeleton compared using Tract-based Spatial Statistics (TBSS), with adjustment for postmenstrual age at birth and at MRI, and MRI site. Researchers and families were blind to treatment group allocation during data collection and analyses. FINDINGS: Of the 109 babies the demographics of the 49 babies exposed to magnesium sulphate were similar to the 60 babies exposed to placebo. In babies whose mothers were allocated to magnesium sulphate, fractional anisotropy was lower within the corticospinal tracts and corona radiata, the superior and inferior longitudinal fasciculi, and the inferior fronto-occipital fasciculi compared to babies whose mothers were allocated placebo (P < 0·05). INTERPRETATION: In babies born preterm after 30 weeks' gestation, antenatal magnesium sulphate exposure did not promote development of white matter microstructure in pathways affecting motor or cognitive function. This suggests that if the neuroprotective effect of magnesium sulphate treatment prior to preterm birth is confirmed at this gestation, the mechanisms are not related to accelerated white matter maturation inferred from fractional anisotropy. FUNDING: This study was funded by a project grant from the Health Research Council of New Zealand (HRC 14/153).

Photorealistic Depiction of Intracranial Tumors Using Cinematic Rendering of Volumetric 3T MRI Data.

RATIONALE AND OBJECTIVES: Cinematic Rendering (CR) incorporates a complex lightning model that creates photorealistic models from isotropic 3D imaging data. The utility of CR in depicting volumetric MRI data for pre-therapeutic planning is discussed, with intracranial tumors as a demonstrative example. MATERIALS AND METHODS: We present a series of Cinematically Rendered intracranial tumors and discuss their utility in multidisciplinary pre-therapeutic evaluation. Isotropic, high-resolution, volumetric MRI data was collected, and CR was performed utilizing a proprietary application, "Anatomy Education" Siemens, Munich, Germany. RESULTS: Discrimination of cortex to white matter, brain surface to vessels, subarachnoid space to cortex and skull to intracranial structures was achieved and optimized by using various display settings on the Anatomy education application. Progressive removal of tissue layers allowed for a comprehensive assessment of the entire region of interest. Complex, small structures were demonstrated in very high detail. The depth and architecture of the sulci was appreciated in a format that more closely mimicked gross pathology than traditional imaging modalities. With appropriate display settings, the relationship of the cortical surface to the adjacent vasculature was also delineated. CONCLUSION: CR depicts the anatomic location of brain tumors in a format that depicts the relative proximity of adjacent structures in all dimensions and degrees of freedom. This allows for better conceptualization of the pathology and greater ease of communication between radiologists and other clinical teams, especially in the context of pretherapeutic planning.

Spatial variation of perfusion MRI reflects cognitive decline in mild cognitive impairment and early dementia.

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer's dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer's disease.

Multiple cerebral cavernous hemangiomas masquerading as hemorrhagic brain metastases.

Intracranial hemorrhagic metastases are a relatively common finding in patients with thyroid carcinoma. Consequently, more unusual vascular lesions may be overlooked in contemplating a differential diagnosis in this patient group. A 50-year-old female with previously treated papillary thyroid carcinoma presented to the emergency department following new onset seizures. Her work up revealed multiple intraparenchymal brain lesions, hyperdense on computed tomography and demonstrating susceptibility effect, T1 shortening and contrast enhancement on magnetic resonance imaging, suggestive of metastases. Subsequent studies revealed lesional architecture consistent with multiple cavernous malformations, made evident by resolution of edema and evolution of blood products. Clinicians should be aware of the possibility of unusual intracranial hemorrhagic lesions in oncology patients which may only become evident on serial imaging evaluation. Cavernous hemangioma has typical MRI characteristic features which includes "mulberry" appearance on T2-weighted and fluid attenuation inversion recovery images with varying internal signal intensity which indicates multiple stages of blood products within the cavernous hamngioma. The lesions commonly have a typical T2-weighted dark hemosiderin rim. Blood sensitive demonstrates prominent surrounding hypointensity representing blooming secondary to internal blood products and/or calcification, if present. Cavernous hemangioma may rarely demonstrate some degree of contrast enhancement. Perfusion imaging may show alteration in capillary permeability involving cavernous malformations which has been previously described in the literature.

Effect of antenatal magnesium sulphate on MRI biomarkers of white matter development at term equivalent age: The magnum study.

BACKGROUND: Magnesium sulphate given to women immediately prior to very preterm birth protects the perinatal brain, so fewer babies die or develop cerebral palsy. How magnesium sulphate exerts these beneficial effects remains uncertain. The aim of the MagNUM Study was to assess the effect of exposure to antenatal magnesium sulphate on MRI measures of brain white matter microstructure at term equivalent age. METHODS: Nested cohort study within the randomised Magnesium sulphate at 30 to <34 weeks' Gestational age Neuroprotection Trial (MAGENTA). Mothers at risk of preterm birth at 30 to <34 weeks' gestation were randomised to receive either 4 g of magnesium sulphate heptahydrate [8 mmol magnesium ions], or saline placebo, infused over 30 min when preterm birth was planned or expected within 24 h. Participating babies underwent diffusion tensor MRI at term equivalent age. The main outcomes were fractional anisotropy across the white matter tract skeleton compared using Tract-based Spatial Statistics (TBSS), with adjustment for postmenstrual age at birth and at MRI, and MRI site. Researchers and families were blind to treatment group allocation during data collection and analyses. FINDINGS: Of the 109 participating babies the demographics of the 60 babies exposed to magnesium sulphate were similar to the 49 babies exposed to placebo. In babies whose mothers were allocated to magnesium sulphate, fractional anisotropy was higher within the corticospinal tracts and corona radiata, the superior and inferior longitudinal fasciculi, and the inferior fronto-occipital fasciculi compared to babies whose mothers were allocated placebo (P < 0.05). INTERPRETATION: In babies born preterm, antenatal magnesium sulphate exposure promotes development of white matter microstructure in pathways affecting both motor and cognitive function. This may be one mechanism for the neuroprotective effect of magnesium sulphate treatment prior to preterm birth. FUNDING: Health Research Council of New Zealand.

An Elusive Case of Mycosis Fungoides: Case Report and Review of the Literature.

Erythroderma refers to a spectrum of skin diseases resulting in diffuse erythema and scaling encompassing ≥ 90% of the body surface area. The differential diagnosis ranges from primary dermatologic diseases such as atopic dermatitis and psoriasis to potentially deadly causes such as staphylococcal toxic shock syndrome, toxic epidermal necrolysis, and malignancy. Cutaneous T cell lymphoma (CTCL) is an uncommon but highly morbid cause of erythroderma. This non-Hodgkin lymphoma remains a diagnostic challenge due to its variable clinical presentation and varied histologic features. Mycosis fungoides (MF) is the most common form of CTCL. Making a timely diagnosis is challenging as it may mimic inflammatory diseases of the skin including eczema, psoriasis, lichen planus, and cutaneous lupus. We present a case of a 58-year-old man who presented with 5 years of cutaneous symptoms and several months of fevers and night sweats, ultimately diagnosed as MF. Owing to diffuse CD30 positivity, he was a candidate for brentuximab vedotin, an antibody-drug conjugate medication that selectively targets the CD30 antigen. This resulted in an excellent therapeutic response.

Percutaneous Microwave Ablation and Cementoplasty: Clinical Utility in the Treatment of Painful Extraspinal Osseous Metastatic Disease and Myeloma.

OBJECTIVE. The purpose of this study was to review the efficacy and durability of pain control and local tumor control using microwave ablation and cementoplasty in treating extraspinal osseous tumors. Painful osseous metastases are a common cause of cancer-related morbidity. Percutaneous thermal ablation presents an attractive minimally invasive option in this vulnerable patient group. MATERIALS AND METHODS. A retrospective review included 65 patients (35 men, 30 women) with 77 tumors who underwent image-guided microwave ablation and cementoplasty at a tertiary referral academic center over 18 months. Procedural efficacy was determined with a visual analog scale before the procedure and 24 hours, 2-4 weeks, and 20-24 weeks after the procedure. Locoregional control was assessed at follow-up cross-sectional imaging. RESULTS. The 77 tumors were in the following locations: ilium, 38; acetabulum on supraacetabular region, 23; femur, five; humerus, four; shoulder, four; sternum, three. The tumors were 15 multiple myelomas and metastases from cancers of the following organs: colon, nine; lung, 15; breast, 12; thyroid, seven; prostate, three; and kidney, four. Complete, successful ablation of all 77 tumors was achieved. Mean ablation time was 6 minutes 15 seconds (SD, 12 seconds), and mean energy used was 5.49 (SD, 2.97) kJ. The mean visual analog scale scores were 6.32 (SD, 1.94) before the procedure, 1.01 (SD, 1.24) at 24 hours, 1.71 (SD, 1.31) at 2-4 weeks, and 2.01 (SD, 1.42) at 20-24 weeks. Follow-up imaging at 20-24 weeks showed no local progression in 42 of 65 patients (64.6%). Six patients died 24-52 weeks after the procedure. No procedure-related complications were reported. CONCLUSION. Microwave ablation is efficacious in alleviating pain due to osseous metastases. The modality has promise for locoregional control of metastases, particularly in the context of oligometastatic (limited disseminated) disease.

Image guided percutaneous spine procedures using an optical see-through head mounted display: proof of concept and rationale.

BACKGROUND AND PURPOSE: Optical see-through head mounted displays (OST-HMDs) offer a mixed reality (MixR) experience with unhindered procedural site visualization during procedures using high resolution radiographic imaging. This technical note describes our preliminary experience with percutaneous spine procedures utilizing OST-HMD as an alternative to traditional angiography suite monitors. METHODS: MixR visualization was achieved using the Microsoft HoloLens system. Various spine procedures (vertebroplasty, kyphoplasty, and percutaneous discectomy) were performed on a lumbar spine phantom with commercially available devices. The HMD created a real time MixR environment by superimposing virtual posteroanterior and lateral views onto the interventionalist's field of view. The procedures were filmed from the operator's perspective. Videos were reviewed to assess whether key anatomic landmarks and materials were reliably visualized. Dosimetry and procedural times were recorded. The operator completed a questionnaire following each procedure, detailing benefits, limitations, and visualization mode preferences. RESULTS: Percutaneous vertebroplasty, kyphoplasty, and discectomy procedures were successfully performed using OST-HMD image guidance on a lumbar spine phantom. Dosimetry and procedural time compared favorably with typical procedural times. Conventional and MixR visualization modes were equally effective in providing image guidance, with key anatomic landmarks and materials reliably visualized. CONCLUSION: This preliminary study demonstrates the feasibility of utilizing OST-HMDs for image guidance in interventional spine procedures. This novel visualization approach may serve as a valuable adjunct tool during minimally invasive percutaneous spine treatment.

Virtual Reality in Neurointervention.

OBJECTIVES: Virtual reality (VR) allows users to experience realistic, immersive 3D virtual environments with the depth perception and binocular field of view of real 3D settings. Newer VR technology has now allowed for interaction with 3D objects within these virtual environments through the use of VR controllers. This technical note describes our preliminary experience with VR as an adjunct tool to traditional angiographic imaging in the preprocedural workup of a patient with a complex pseudoaneurysm. METHODS: Angiographic MRI data was imported and segmented to create 3D meshes of bilateral carotid vasculature. The 3D meshes were then projected into VR space, allowing the operator to inspect the carotid vasculature using a 3D VR headset as well as interact with the pseudoaneurysm (handling, rotation, magnification, and sectioning) using two VR controllers. RESULTS: 3D segmentation of a complex pseudoaneurysm in the distal cervical segment of the right internal carotid artery was successfully performed and projected into VR. Conventional and VR visualization modes were equally effective in identifying and classifying the pathology. VR visualization allowed the operators to manipulate the dataset to achieve a greater understanding of the anatomy of the parent vessel, the angioarchitecture of the pseudoaneurysm, and the surface contours of all visualized structures. CONCLUSION: This preliminary study demonstrates the feasibility of utilizing VR for preprocedural evaluation in patients with anatomically complex neurovascular disorders. This novel visualization approach may serve as a valuable adjunct tool in deciding patient-specific treatment plans and selection of devices prior to intervention.

Treatment of hemorrhagic head and neck lesions by direct puncture and n-BCA embolization.

Life-threatening bleeding in the head and neck region requires urgent management. These hemorrhagic lesions, for example, a ruptured pseudoaneurysm, are often treated by transarterial embolization (TAE), but prior intervention or surgery, inflammation, anatomic variants, and vessel tortuosity may render an endovascular approach challenging, time-consuming, and sometimes impossible. We report two cases of severe head and neck hemorrhages successfully embolized with n-butyl cyanoacrylate via direct puncture, and propose this approach as a fast, safe, and effective alternative to TAE.

Treatment of hemorrhagic head and neck lesions by direct puncture and nBCA embolization.

Life-threatening bleeding in the head and neck region requires urgent management. These hemorrhagic lesions, for example, a ruptured pseudoaneurysm, are often treated by transarterial embolization (TAE), but prior intervention or surgery, inflammation, anatomic variants, and vessel tortuosity may render an endovascular approach challenging, time-consuming, and sometimes impossible. We report two cases of severe head and neck hemorrhages successfully embolized with n-butyl cyanoacrylate via direct puncture, and propose this approach as a fast, safe, and effective alternative to TAE.