Charles L. Truwit

Posterior reversible encephalopathy syndrome: Incidence of atypical regions of involvement and imaging findings

OBJECTIVE Posterior reversible encephalopathy syndrome (PRES) is classically characterized as symmetric parietooccipital edema but may occur in other distributions with varying imaging appearances. This study determines the incidence of atypical and typical regions of involvement and unusual imaging manifestations. MATERIALS AND METHODS Seventy-six patients were eventually included as having confirmed PRES from 111 initially suspected cases, per imaging and clinical follow-up. Two neuroradiologists retrospectively reviewed each MR image. Standard sequences were unenhanced FLAIR and T1- and T2-weighted images in all patients, with diffusion-weighted imaging (n = 75) and contrast-enhanced T1-weighted imaging (n = 69) in most. The regions involved were recorded on the basis of FLAIR findings, and the presence of atypical imaging findings (contrast enhancement, restricted diffusion, hemorrhage) was correlated with the severity (extent) of hyperintensity or mass effect on FLAIR. RESULTS The incidence of regions of involvement was parietooccipital, 98.7%; posterior frontal, 78.9%; temporal, 68.4%; thalamus, 30.3%; cerebellum, 34.2%; brainstem, 18.4%; and basal ganglia, 11.8%. The incidence of less common manifestations was enhancement, 37.7%; restricted diffusion, 17.3%; hemorrhage, 17.1%; and a newly described unilateral variant, 2.6%. Poor correlation was found between edema severity and enhancement (r = 0.072), restricted diffusion (r = 0.271), hemorrhage (r = 0.267), blood pressure (systolic, r = 0.13; diastolic, r = 0.02). Potentially new PRES causes included contrast-related anaphylaxis and alcohol withdrawal. CONCLUSION This large series of PRES cases shows that atypical distributions and imaging manifestations of PRES have a higher incidence than commonly perceived, and atypical manifestations do not correlate well with the edema severity.

A Generic Framework for Non-rigid Registration Based on Non-uniform Multi-level Free-Form Deformations

This work presents a framework for non-rigid registration which extends and generalizes a previously developed technique by Rueckert et al. [1]. We combine multi-resolution optimization with free-form deformations (FFDs) based on multi-level B-splines to simulate a non-uniform control point distribution. We have applied this to a number of different medical registration tasks to demonstrate its wide applicability, including interventional MRI brain tissue deformation compensation, breathing motion compensation in liver MRI, intra-modality inter-modality registration of pre-operative brain MRI to CT electrode implant data, and inter-subject registration of brain MRI. Our results demonstrate that the new algorithm can successfully register images with an improved performance, while achieving a significant reduction in run-time.

Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy

Background Persons with type 2 diabetes (T2D) are at risk for cognitive impairment and brain atrophy. The ACCORD Memory in Diabetes (MIND) Study investigated whether persons randomized to an intensive glycaemic therapeutic strategy targeting HbA1c to <6% had better cognitive function and a larger brain volume at 40 months than persons randomized to a standard strategy targeting HbA1c to 7%–7.9%.BACKGROUND People with type 2 diabetes are at risk of cognitive impairment and brain atrophy. We aimed to compare the effects on cognitive function and brain volume of intensive versus standard glycaemic control. METHODS The Memory in Diabetes (MIND) study was done in 52 clinical sites in North America as part of Action to Control Cardiovascular Risk in Diabetes (ACCORD), a double two-by-two factorial parallel group randomised trial. Participants (aged 55-80 years) with type 2 diabetes, high glycated haemoglobin A(1c) (HbA(1c)) concentrations (>7·5%; >58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive glycaemic control targeting HbA(1c) to less than 6·0% (42 mmol/mol) or a standard strategy targeting HbA(1c) to 7·0-7·9% (53-63 mmol/mol). Randomisation was via a centralised web-based system and treatment allocation was not masked from clinic staff or participants. We assessed our cognitive primary outcome, the Digit Symbol Substitution Test (DSST) score, at baseline and at 20 and 40 months. We assessed total brain volume (TBV), our primary brain structure outcome, with MRI at baseline and 40 months in a subset of participants. We included all participants with follow-up data in our primary analyses. In February, 2008, raised mortality risk led to the end of the intensive treatment and transition of those participants to standard treatment. We tested our cognitive function hypotheses with a mixed-effects model that incorporated information from both the 20 and 40 month outcome measures. We tested our MRI hypotheses with an ANCOVA model that included intracranial volume and factors used to stratify randomisation. This study is registered with ClinicalTrials.gov, number NCT00182910. FINDINGS We consecutively enrolled 2977 patients (mean age 62·5 years; SD 5·8) who had been randomly assigned to treatment groups in the ACCORD study. Our primary cognitive analysis was of patients with a 20-month or 40-month DSST score: 1378 assigned to receive intensive treatment and 1416 assigned to receive standard treatment. Of the 614 patients with a baseline MRI, we included 230 assigned to receive intensive treatment and 273 assigned to receive standard treatment in our primary MRI analysis at 40 months. There was no significant treatment difference in mean 40-month DSST score (difference in mean 0·32, 95% CI -0·28 to 0·91; p=0·2997). The intensive-treatment group had a greater mean TBV than the standard-treatment group (4·62, 2·0 to 7·3; p=0·0007). INTERPRETATION Although significant differences in TBV favoured the intensive treatment, cognitive outcomes were not different. Combined with the non-significant effects on other ACCORD outcomes, and increased mortality in participants in the intensive treatment group, our findings do not support the use of intensive therapy to reduce the adverse effects of diabetes on the brain in patients with similar characteristics to those of our participants. FUNDING US National Institute on Aging and US National Heart, Lung, and Blood Institute.

Safety, efficacy, and functionality of high-field strength interventional magnetic resonance imaging for neurosurgery

OBJECTIVE Interventional magnetic resonance imaging (MRI) allows neurosurgeons to interactively perform surgery using MRI guidance. High-field strength (1.5-T) imaging permits exceptional observation of intracranial and spinal pathological features. The development of this technology and its application to a variety of neurosurgical procedures are described. METHODS We report on the first 101 cases that were treated in the interventional MRI unit (between January 1997 and September 1998). These cases included 39 brain biopsies, 30 tumor resections, 9 functional neurosurgical cases, 8 cyst drainages, 5 laminectomies, and 10 miscellaneous cases. Patients ranged in age from 14 months to 84 years (median, 43 yr); 61 patients were male and 40 were female. Intraoperative functional techniques that were used to influence surgical decision-making included magnetic resonance spectroscopy, functional MRI, magnetic resonance angiography and venography, chemical shift imaging, and diffusion-weighted imaging. All surgery was performed using MRI-compatible instruments within the 5-gauss line and conventional instruments outside that line. RESULTS All 39 brain biopsies yielded diagnostic tissue. Of the 30 tumor resections, 24 (80%) were considered radiographically complete. The incidence of serious complications was low and was comparable to that associated with conventional operating rooms. One patient developed a Propionibacterium acnes brain abscess 6 weeks after surgery and another patient experienced Staphylococcus aureus scalp cellulitis after a brain biopsy, yielding an infection rate of less than 2%. No clinically significant hemorrhage was observed in immediate postoperative imaging scans, although one patient developed a delayed hematoma after a thalamotomy. One patient experienced a stroke after resection of a hippocampal tumor. No untoward events were associated with MRI-compatible instrumentation or intraoperative patient monitoring. CONCLUSION High-field (1.5-T) interventional MRI is a safe and effective technology for assisting neurosurgeons in achieving the goals of surgery. Preliminary results suggest that the functional capabilities of this technology can yield data that can significantly influence intraoperative neurosurgical decision-making. The rates of serious complications, such as infection, associated with this new technology were low.

Functional neuroanatomy of spatial working memory in children.

Functional magnetic resonance imaging (fMRI) was used to examine spatial working memory in 8- to 11-year-old children tested under three conditions. In the visual condition, children were asked to examine the location of a dot on a screen. In the motor condition, children were instructed to push a button that corresponded to the location of a dot presented on a screen. In the memory condition, children were asked to remember the location of a dot presented 1 or 2 trials previously. Subtracting the activation of the motor condition from the memory condition revealed activity in the dorsal aspects of the prefrontal cortex and in the posterior parietal and anterior cingulate cortex. These findings were also obtained in the analysis of the memory minus visual conditions except that motor cortex activation was also observed. These findings parallel those reported in comparable studies of adults and suggest that fMRI may be a useful means of examining function-structure relations in developmental populations.

X-linked malformations of neuronal migration

Malformations of neuronal migration such as lissencephaly (agyria-pachygyria spectrum) are wellknown causes of mental retardation and epilepsy that are often genetic. For example, isolated lissencephaly sequence and Miller-Dieker syndrome are caused by deletions involving a lissencephaly gene in chromosome 17p13.3, while many other malformation syndromes have autosomal recessive inheritance. In this paper, we review evidence supporting the existence of two distinct X-linked malformations of neuronal migration. X-linked lissencephaly and subcortical band heterotopia (XLIS) presents with sporadic or familial mental retardation and epilepsy. The brain malformation varies from classical lissencephaly, which is observed in males, to subcortical band heterotopia, which is observed primarily in females. The XLIS gene is located in chromosome Xq22.3 based on the breakpoint of an X-autosomal translocation. Bilateral periventricular nodular heterotopia (BPNH) usually presents with sporadic or familial epilepsy with normal intelligence, primarily in females, although we have evaluated two boys with BPNH and severe mental retardation. The gene for BPNH has been mapped to chromosome Xq28 based on linkage studies in multiplex families and observation of a subtle structural abnormality in one of the boys with BPNH and severe mental retardation. NEUROLOGY 1996;47: 331-339

Differences in the gyral pattern distinguish chromosome 17–linked and X-linked lissencephaly

Background: Classical lissencephaly or “smooth brain” is a human brain malformation that consists of diffuse agyria and pachygyria. Two genes associated with classical lissencephaly have recently been cloned—LIS1 from chromosome 17p13.3 and XLIS (also called DCX) from Xq22.3-q23. Objective: We performed genotype-phenotype analysis in children with lissencephaly associated with mutations of different genes. Methods: We compared the phenotype, especially brain imaging studies, in a series of 48 children with lissencephaly, including 12 with Miller-Dieker syndrome (MDS), which is associated with large deletions of LIS1 and other genes in the region, 24 with isolated lissencephaly sequence caused by smaller LIS1 deletions or mutations, and 12 with isolated lissencephaly sequence caused by XLIS mutations. Results: We found consistent differences in the gyral patterns, with the malformation more severe posteriorly in individuals with LIS1 mutations and more severe anteriorly in individuals with XLIS mutations. Thus, mutations of LIS1 are associated with a posterior-to-anterior gradient of lissencephaly, whereas mutations of XLIS are associated with an anterior-to-posterior gradient. We also confirmed differences in severity between MDS and ILS17. Hypoplasia of the cerebellar vermis proved to be more common with XLIS mutations. Conclusion: It is often possible to predict the gene mutation from careful review of brain imaging studies.

Investigation of intraoperative brain deformation using a 1.5-T interventional MR system: preliminary results

All image-guided neurosurgical systems that the authors are aware of assume that the head and its contents behave as a rigid body. It is important to measure intraoperative brain deformation (brain shift) to provide some indication of the application accuracy of image-guided surgical systems, and also to provide data to develop and validate nonrigid registration algorithms to correct for such deformation. The authors are collecting data from patients undergoing neurosurgery in a high-field (1.5 T) interventional magnetic resonance (MR) scanner. High-contrast and high-resolution gradient-echo MR image volumes are collected immediately prior to surgery, during surgery, and at the end of surgery, with the patient intubated and lying on the operating table in the operative position. Here, the authors report initial results from six patients: one freehand biopsy, one stereotactic functional procedure, and four resections. The authors investigate intraoperative brain deformation by examining threshold boundary overlays and difference images and by measuring ventricular volume. They also present preliminary results obtained using a nonrigid registration algorithm to quantify deformation. They found that some cases had much greater deformation than others, and also that, regardless of the procedure, there was very little deformation of the midline, the tentorium, the hemisphere contralateral to the procedure, and ipsilateral structures except those that are within 1 cm of the lesion or are gravitationally above the surgical site.

Brain biopsy using high-field strength interventional magnetic resonance imaging

OBJECTIVE Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance imaging (MRI) now allows neurosurgeons to interactively investigate specific regions, with exquisite observational detail. We evaluated the safety and efficacy of this new surgical approach. METHODS Between January 1997 and June 1998, 35 brain biopsies were performed in a high-field strength interventional MRI unit. All biopsies were performed using MRI-compatible instrumentation. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathological examination of the biopsy specimens was performed to verify the presence of diagnostic tissue, and intra- and postoperative imaging was performed to exclude the presence of intraoperative hemorrhage. Recently, magnetic resonance spectroscopic targeting was used for six patients. RESULTS Diagnostic tissue was obtained in all 35 brain biopsies and was used in therapeutic decision-making. Histological diagnoses included 28 primary brain tumors (12 glioblastomas multiforme, 9 oligodendrogliomas, 2 anaplastic astrocytomas, 2 astrocytomas, 1 lymphoma, and 1 anaplastic oligodendroglioma), 1 melanoma brain metastasis, 1 cavernous sinus meningioma, 1 cerebral infarction, 1 demyelinating process, and 3 cases of radiation necrosis. In all cases, magnetic resonance spectroscopy was accurate in distinguishing recurrent tumors (five cases) from radiation necrosis (one case). No patient sustained clinically or radiologically significant hemorrhage, as determined by intraoperative imaging performed immediately after the biopsy. One patient (3%) suffered transient hemiparesis after a pontine biopsy for investigation of a brain stem glioma. Another patient developed scalp cellulitis, with possible intracranial extension, 3 weeks after the biopsy; this condition was effectively treated with antibiotic therapy. Three patients were discharged on the day of the biopsy. CONCLUSION Interventional 1.5-T MRI is a safe and effective method for evaluating lesions of the brain. Magnetic resonance spectroscopic targeting is likely to augment the diagnostic yield of brain biopsies.

Measurement and analysis of brain deformation during neurosurgery

Recent studies have shown that the surface of the brain is deformed by up to 20 mm after the skull is opened during neurosurgery, which could lead to substantial error in commercial image-guided surgery systems. We quantitatively analyze the intraoperative brain deformation of 24 subjects to investigate whether simple rules can describe or predict the deformation. Interventional magnetic resonance images acquired at the start and end of the procedure are registered nonrigidly to obtain deformation values throughout the brain. Deformation patterns are investigated quantitatively with respect to the location an magnitude of deformation, and to the distribution and principal direction of the displacements. We also measure the volume change of the lateral ventricles by manual segmentation. Our study indicates that brain shift occurs predominantly in the hemisphere ipsi-lateral to the craniotomy, and that there is more brain deformation during resection procedures than during biopsy or functional procedures. However, the brain deformation patterns are extremely complex in this group of subjects. This paper quantitatively demonstrates that brain deformation occurs not only at the surface, but also in deeper brain structure, and that the principal direction of displacement does not always correspond with the direction of gravity. Therefore, simple computational algorithms that utilize limited intraoperative information (e.g., brain surface shift) will not always accurately predict brain deformation at the lesion.