Robert Stahl

White and gray matter abnormalities in the brain of patients with fibromyalgia: A diffusion‐tensor and volumetric imaging study

OBJECTIVE To use a combination of magnetic resonance diffusion-tensor imaging (MR-DTI) and MR imaging of voxel-based morphometry (MR-VBM) in patients with fibromyalgia syndrome (FMS) to determine microstructural and volume changes in the central neuronal networks involved in the sensory-discriminative and affective-motivational characteristics of pain, anxiety, memory, and regulation of the stress response. METHODS Thirty female patients with FMS and 30 healthy female control subjects were studied. Predefined areas of the brain were measured for volume of gray matter by MR-VBM and for diffusivity and fractional anisotropy (FA) by MR-DTI. Higher FA values and reduced diffusivity are thought to reflect increased complexity of brain-tissue microstructure. RESULTS MR-VBM and MR-DTI demonstrated a striking pattern of changes in brain morphology in patients with FMS. Both thalami, the thalamocortical tracts, and both insular regions showed significant decreases in FA. In contrast, increases in FA and decreases in gray matter volume were seen in the postcentral gyri, amygdalae, hippocampi, superior frontal gyri, and anterior cingulate gyri. Increased pain intensity scores were correlated with changes in MR-DTI measurements in the right superior frontal gyrus. Increased fatigue was correlated with changes in the left superior frontal and left anterior cingulate gyrus, and self-perceived physical impairment was correlated with changes in the left postcentral gyrus. Higher intensity scores for stress symptoms were correlated negatively with diffusivity in the thalamus and FA in the left insular cortex. No relationship was found between MR-VBM measurements and symptom intensity scores. CONCLUSION MR-DTI allows the visualization of microstructural changes in the brain of patients with FMS, appears to be more sensitive than MR-VBM, and may serve as an additional diagnostic technique in FMS and probably other dysfunctional pain syndromes.

Multivariate network analysis of fiber tract integrity in Alzheimer’s disease

Axonal and dendritic integrity is affected early in Alzheimers disease (AD). Studies using region of interest or voxel-based analysis of diffusion tensor imaging data found significant decline of fractional anisotropy, a marker of fiber tract integrity, in selected white matter areas. We applied a multivariate network analysis based on principal component analysis to fractional anisotropy maps derived from diffusion-weighted scans from 15 AD patients, and 14 elderly healthy controls. Fractional anisotropy maps were obtained from an EPI diffusion sequence using parallel imaging to reduce distortion artifacts. We used high-dimensional image warping to control for partial volume effects due to white matter atrophy in AD. We found a significant regional pattern of fiber changes (p < 0.01) indicating that the integrity of intracortical projecting fiber tracts (including corpus callosum, cingulum and fornix, and frontal, temporal and occipital lobe white matter areas) was reduced, whereas extracortical projecting fiber tracts, including the pyramidal and extrapyramidal systems and somatosensory projections, were relatively preserved in AD. Effects of a univariate analysis were almost entirely contained within the multivariate effect. Our findings illustrate the use of a multivariate approach to fractional anisotropy data that takes advantage of the highly organized structure of anisotropy maps, and is independent of multiple comparison correction and partial volume effects. In agreement with post-mortem evidence, our study demonstrates dissociation between intracortical and extracortical projecting fiber systems in AD in the living human brain.

Spatial analysis of magnetic resonance and relaxation times improves classification between subjects with and without osteoarthritis

PURPOSE Studies have shown that functional analysis of knee cartilage based on magnetic resonance (MR) relaxation times is a valuable tool in the understanding of osteoarthritis (OA). In this work, the regional spatial distribution of knee cartilage T1rho, and T2 relaxation times based on texture and laminar analyses was studied to investigate if they provide additional insight compared to global mean values in the study of OA. METHODS Knee cartilage of 36 subjects, 19 healthy controls and 17 with mild OA, was divided into 16 compartments. T1rho and T2 relaxation times were studied with first order statistics, eight texture parameters with four different orientations using gray-level co-occurrence matrices and by subdividing each compartment into two different layers: Deep and superficial. Receiver operating characteristic curve analysis was performed to evaluate the potential of each technique to correctly classify the populations. RESULTS Although the deep and superficial cartilage layers had in general significantly different T1rho and T2 relaxation times, they performed similarly in terms of subject discrimination. The subdivision of lateral and medial femoral compartments into weight-bearing and non-weight-bearing regions did not improve discrimination. Also it was found that the most sensitive region was the patella and that T1rho discriminated better than T2. The most important finding was that with respect to global mean values, laminar and texture analyses improved subject discrimination. CONCLUSIONS Results of this study suggest that spatially assessing MR images of the knee cartilage relaxation times using laminar and texture analyses could lead to better and probably earlier identification of cartilage matrix abnormalities in subjects with OA.

Magnetic resonance imaging-guided focused ultrasound treatment of symptomatic uterine fibroids: impact of technology advancement on ablation volumes in 115 patients.

ObjectivesThe aim of this study was to assess the impact of the advanced technology of the new ExAblate 2100 system (Insightec Ltd, Haifa, Israel) for magnetic resonance imaging (MRI)–guided focused ultrasound surgery on treatment outcomes in patients with symptomatic uterine fibroids, as measured by the nonperfused volume ratio. Materials and MethodsThis is a retrospective analysis of 115 women (mean age, 42 years; range, 27–54 years) with symptomatic fibroids who consecutively underwent MRI-guided focused ultrasound treatment in a single center with the new generation ExAblate 2100 system from November 2010 to June 2011. Mean ± SD total volume and number of treated fibroids (per patient) were 89 ± 94 cm3 and 2.2 ± 1.7, respectively. Patient baseline characteristics were analyzed regarding their impact on the resulting nonperfused volume ratio. ResultsMagnetic resonance imaging–guided focused ultrasound treatment was technically successful in 115 of 123 patients (93.5%). In 8 patients, treatment was not possible because of bowel loops in the beam pathway that could not be mitigated (n = 6), patient movement (n = 1), and system malfunction (n = 1). Mean nonperfused volume ratio was 88% ± 15% (range, 38%-100%). Mean applied energy level was 5400 ± 1200 J, and mean number of sonications was 74 ± 27. No major complications occurred. Two cases of first-degree skin burn resolved within 1 week after the intervention. Of the baseline characteristics analyzed, only the planned treatment volume had a statistically significant impact on nonperfused volume ratio. ConclusionsWith technological advancement, the outcome of MRI-guided focused ultrasound treatment in terms of the nonperfused volume ratio can be enhanced with a high safety profile, markedly exceeding results reported in previous clinical trials.

Paramagnetic thermosensitive liposomes for MR-thermometry

MR-thermometry methods have been developed for the guidance and control of thermal therapies such as thermal ablation or regional hyperthermia. However, they are limited to the measurement of temperature changes and, thus, cannot be used to assess absolute temperature values. Paramagnetic thermosensitive liposomes are innovative contrast agents offering the potential to overcome these limitations. They are composed of a gadolinium- or manganese-based compound enclosed by a phospholipid membrane with a distinct gel-to-liquid crystalline phase transition temperature (Tm). At this temperature, the phospholipid membrane changes from a gel-phase to a liquid-crystalline phase which is associated with an increased transmembrane permeability towards solutes and water. Under these conditions, both types of paramagnetic thermosensitive liposomes demonstrate a significant increase in longitudinal (T1) relaxivity, attributed to the release of paramagnetic material from the liposome and/or to the increased water exchange rate between the liposome interior and exterior. Paramagnetic thermosensitive liposomes have already been successfully studied in animal models and have demonstrated a clear correlation between tissue temperature changes and signal intensity changes in MRI. Nevertheless, before entering clinical trials they have to be studied in more detail with regard to dose, pharmacokinetics and toxicity.

Anisotropy of callosal motor fibers in combination with transcranial magnetic stimulation in the course of motor development.

Objectives:The corpus callosum (CC) represents a key structure for hand motor development and is accessible to investigation by diffusion tensor magnetic resonance imaging (DTI) and transcranial magnetic stimulation (TMS). To identify quantifiable markers for motor development, we combined DTI with TMS. Materials and Methods:We examined groups of 11 healthy preschool-aged children, 10 healthy adolescents, and 10 healthy adults with both, DTI and TMS/ipsilateral silent period (iSP). DTI-values for fractional anisotropy (FA) were calculated for areas I to V of the CC. ISP-values for latency, duration, and extent of electromyography suppression were calculated. Results:FA was significantly lower in areas II to IV of the CC in children as compared with adults (P < 0.05). In area III, where callosal motor fibers cross the CC, FA differed significantly between children and adolescents (P < 0.05). TMS parameters demonstrated significant age-related differences in duration and extent of iSP (P < 0.05). No significant differences were detected regarding latency of iSP. Conclusions:The maturation of callosal motor fiber connectivity seems to reflect the degree of interhemispheric inhibition between the motor cortices with anisotropy of callosal motor fibers being a potential marker for motor development.

Development of Hypertension is Less Frequent after Bilateral Nephron Sparing Surgery for Bilateral Wilms Tumor in a Long-Term Survey

PURPOSE The option of nephron sparing surgery for unilateral Wilms tumor has been debated in the recent literature. This procedure is being used increasingly to preserve kidney tissue and function. However, nephron sparing surgery is feasible only for selected cases, and a higher local relapse rate has been observed. Moreover, a significant reduction of nephrons is associated with development of renal hypertension and progressive renal failure. We analyzed outcomes after bilateral partial nephrectomy and unilateral partial plus contralateral total nephrectomy in patients with bilateral Wilms tumor. MATERIALS AND METHODS We analyzed data from the Society of Pediatric Oncology and Hematology database on 22 patients with bilateral Wilms tumor. Kidney size was measured using volumetric analysis of magnetic resonance imaging. Patients were matched with children who had undergone magnetic resonance imaging of the abdomen for other malignancies. RESULTS Mean kidney volumes after unilateral partial plus total contralateral nephrectomy (66.9 cm(3)) were significantly greater than the reference kidneys (p = 0.028), whereas controls were equal to the bilateral partial nephrectomy group (49.7 cm(3), p = 0.959). Total kidney volume was significantly larger after bilateral partial nephrectomy (102.1 cm(3)) vs unilateral partial plus total contralateral nephrectomy (66.9 cm(3), p = 0.0338). Eight patients (66.7%) had renal hypertension after unilateral partial plus total contralateral nephrectomy but only 2 (20%) after bilateral partial nephrectomy (p = 0.043). Overall survival and relapse rates were equal between the groups and did not correlate with unfavorable histology. CONCLUSIONS Our findings suggest that patients with bilateral Wilms tumor benefit from bilateral nephron sparing surgery. Hypertension is less common after bilateral partial nephrectomy, and rates of local relapse or disease associated death are distributed equally between the groups.

CT Fluoroscopy-Guided Percutaneous Fiducial Marker Placement for CyberKnife Stereotactic Radiosurgery: Technical Results and Complications in 222 Consecutive Procedures

PURPOSE To evaluate technical outcome and safety of computed tomographic (CT) fluoroscopy-guided percutaneous fiducial marker placement before CyberKnife stereotactic radiosurgery. MATERIALS AND METHODS Retrospective analysis was performed of 196 patients (106 men) undergoing CT fluoroscopy-guided fiducial marker placement in 222 consecutive procedures under local anesthesia from March 2006 to February 2012. Technical success was defined as fiducial marker location in the tumor or vicinity suitable for CyberKnife radiosurgery evaluated on postinterventional planning CT. Complications were classified per Society of Interventional Radiology (SIR). RESULTS One hundred ninety-six patients (age, 61.5 y ± 13.1) underwent percutaneous placement of 321 fiducial markers (mean per tumor, 1.2 ± 0.5; range, 1-4) in 37 primary tumors and 227 metastases in the thorax (n = 121), abdomen (n = 122), and bone (n = 21). Fiducial marker placement was technically successful in all procedures: intratumoral localization in 193 (60.1%), at tumor margin in 50 (15.6%), and outside of tumor in 78 cases (24.3%; mean distance to marker, 0.4 cm ± 0.6; range, 0-2.9 cm). Complications were observed in 63 placement procedures (28.4%), including minor self-limiting pneumothorax (n = 21; SIR class B) and self-limiting pulmonary hemorrhage (n = 35; SIR class A), and major pneumothorax requiring thoracostomy/drainage insertion (n = 14; SIR class D) and systemic toxicity of local anesthetic drug (n = 1; SIR class D). CONCLUSIONS CT fluoroscopy-guided percutaneous fiducial marker placement can be performed with high technical success under local anesthesia in various anatomic regions. Although self-limiting in most cases, pneumothorax and pulmonary hemorrhage are frequently observed during fiducial marker implantation into lung tumors.

Left Frontal Hub Connectivity during Memory Performance Supports Reserve in Aging and Mild Cognitive Impairment

Reserve in aging and Alzheimer’s disease (AD) is defined as maintaining cognition at a relatively high level in the presence of neurodegeneration, an ability often associated with higher education among other life factors. Recent evidence suggests that higher resting-state functional connectivity within the frontoparietal control network, specifically the left frontal cortex (LFC) hub, contributes to higher reserve. Following up these previous resting-state fMRI findings, we probed memory-task related functional connectivity of the LFC hub as a neural substrate of reserve. In elderly controls (CN, n = 37) and patients with mild cognitive impairment (MCI, n = 17), we assessed global connectivity of the LFC hub during successful face-name association learning, using generalized psychophysiological interaction analyses. Reserve was quantified as residualized memory performance, accounted for gender and proxies of neurodegeneration (age, hippocampus atrophy, and APOE genotype). We found that greater education was associated with higher LFC-connectivity in both CN and MCI during successful memory. Furthermore, higher LFC-connectivity predicted higher residualized memory (i.e., reserve). These results suggest that higher LFC-connectivity contributes to reserve in both healthy and pathological aging.

CT fluoroscopy-guided percutaneous vertebroplasty in patients with multiple myeloma: analysis of technical results from 44 sessions with 67 vertebrae treated

PURPOSE This study aimed to assess the results of computed tomography (CT) fluoroscopy-guided vertebroplasty in patients with multiple myeloma, focusing on the frequency and clinical impact of polymethylmethacrylate (PMMA) leaks. MATERIALS AND METHODS From December 2001 to August 2008, 39 patients (17 females, 22 males; mean age, 65±7 years) with multiple myeloma suffering from painful spinal osteolyses underwent vertebroplasty. A total of 67 vertebrae were treated in 44 sessions under CT fluoroscopy (single-slice, 4-row CT, and 16-row CT). In the planning CT scan, osteolytic destruction (i.e., none, ≤25%, ≤50%, ≤75%, or ≤100%) was assessed regarding the vertebral cross-sectional area, the cortical border of the spinal canal, and the outer circumference. CT performed after vertebroplasty was used to detect local PMMA leaks. Patient charts were retrospectively reviewed with special respect to peri and postinterventional adverse events. Clinical outcomes were assessed on a visual analog scale (VAS) 24 hours before, 24 hours after, and 6 months after vertebroplasty. RESULTS Overall, 37.3%, 12.0%, and 6.0% of vertebrae showed at least 50% osteolytic involvement of the cross-sectional area, spinal canal, and outer vertebral cortex, respectively. Intradiscal, intraspinal, paravertebral, and intercostovertebral/posterolateral leaks were seen in 21.6%, 35.1%, 43.3%, and 0% of vertebrae, respectively. The ratio of basivertebral to segmental venous leaks was 16.2%/40.5%. No major complications occurred. The mean VAS score decreased significantly (P < 0.05) from 6.4 at 24 hours before vertebroplasty to 3.2 at a mean follow-up of 9.0 months. CONCLUSION Vertebroplasty in multiple myeloma can be performed safely under CT fluoroscopy, even with substantial destruction of the vertebral cross-sectional area or cortical bone. A high clinical success rate was achieved, regardless of whether PMMA leaks were present.