Meir Faibel

Magnetic resonance imaging-guided, high-intensity focused ultrasound for brain tumor therapy

OBJECTIVEMagnetic resonance imaging-guided high-intensity focused ultrasound (MRIgFUS) is a novel technique that may have the potential for precise image-guided thermocoagulation of intracranial lesions. The system delivers small volumetric sonications from an ultrasound phased array transmitter that focuses energy selectively to destroy the target with verification by magnetic resonance imaging-generated thermal maps. A Phase I clinical study was initiated to treat patients with recurrent glioma with MRIgFUS. METHODSTo date, three patients with histologically verified recurrent glioblastoma multiforme have been treated with MRIgFUS. All patients underwent craniectomy 7 to 10 days before therapy to create a bony window for the ultrasound treatment. Sonications were applied to induce thermocoagulation of the enhancing tumor mass. Long-term radiological follow-up and post-treatment tissue specimens were available for all patients. RESULTSMRIgFUS treatment resulted in immediate changes in contrast-enhanced T1-, T2-, and diffusion-weighted magnetic resonance imaging scans in the treated regions with subsequent histological evidence of thermocoagulation. In one patient, heating of brain tissue in the sonication path resulted in a secondary focus outside the target causing neurological deficit. New software modifications were developed to address this problem. CONCLUSIONIn this first clinical report, MRIgFUS was demonstrated to be a potentially effective means of destroying tumor tissue by thermocoagulation, although with an associated morbidity and the inherent invasive nature of the procedure requiring creation of a bone window. A modified technology to allow MRIgFUS treatment through a closed cranium is being developed.

Automated Detection and Characterization of Multiple Sclerosis Lesions in Brain MR Images

In the present study an automatic algorithm for detection and contouring of multiple sclerosis (MS) lesions in brain magnetic resonance (MR) images is introduced. This algorithm automatically detects MS lesions in axial proton density, T2-weighted, gadolinium enhanced, and fast fluid attenuated inversion recovery (FLAIR) brain MR images. Automated detection consists of three main stages: (1) detection and contouring of all hyperintense signal regions within the image; (2) partial elimination of false positive segments (defined herein as artifacts) by size, shape index, and anatomical location; (3) the use of an artificial neural paradigm (Back-Propagation) for final removal of artifacts by differentiating them from true MS lesions. The algorithm was applied to 45 images acquired from 14 MS patients. The algorithms sensitivity was 0.87 and the specificity 0.96. In 34 images, 100% of the lesions were detected. The algorithm potentially may serve as a useful preprocessing tool for quantitative MS monitoring via magnetic resonance imaging.

Magnetic resonance imaging-guided focused ultrasound for thermal ablation in the brain: a feasibility study in a swine model.

INTRODUCTIONMagnetic resonance imaging (MRI)-guided focused ultrasound is a novel technique that was developed to enable precise, image-guided targeting and destruction of tumors by thermocoagulation. The system, ExAblate2000, is a focused ultrasound delivery system embedded within the MRI bed of a conventional diagnostic MRI scanner. The device delivers small volumetric sonications from an ultrasound phased array transmitter that converge energy to selectively destroy the target. Temperature maps generated by the MRI scanner verify the location and thermal rise as feedback, as well as thermal destruction. To assess the safety, feasibility, and precision of this technology in the brain, we have used the ExAblate system to create predefined thermal lesions in the brains of pigs. METHODSTen pigs underwent bilateral craniectomy to provide a bone window for the ultrasound beams. Seven to 10 days later, the animals were anesthetized and positioned in the ExAblate system. A predefined, 1-cm3 frontal para ventricular region was delineated as the target and treated with multiple sonications. MRI was performed immediately and 1 week after treatment. The animals were then sacrificed and the brains removed for pathological study. The size of individual sonication points and the location of the lesion were compared between the planned dose maps, posttreatment MRI scans, and pathological specimen. RESULTSHigh-energy sonications led to precise coagulation necrosis of the specified targets as shown by subsequent MRI, macroscopic, and histological analysis. The thermal lesions were sharply demarcated from the surrounding brain with no anatomic or histological abnormalities outside the target. CONCLUSIONMRI-guided focused ultrasound proved a precise and an effective means to destroy anatomically predefined brain targets by thermocoagulation with minimal associated edema or damage to adjacent structures. Contrast-enhanced T1-, T2-, and diffusion-weighted MRI scans may be used for real-time assessment of tissue destruction.

Alfacalcidol treatment in multiple sclerosis

To the Editor: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. In recent years several immunomodulating drugs have been shown to decrease relapse rate and neurologic disability in relapsing–remitting MS patients by approximately 30%, and thus there is still the need to search for additional interventions (1). 1,25-Dihydroxyvitamin D3 [1,25-D3], the active form of vitamin D, has been shown to prevent clinical signs of experimental autoimmune encephalomyelitis—the animal model of MS. 1,25-D3 also prevents the progression of experimental autoimmune encephalomyelitis when administered with the appearance of the first symptoms of disability, thus affecting the disease process during both the immunization phase and after the onset of clinical signs (2). It was suggested that 1,25-D3 exerts its immunomodulatory effects within the central nervous system during an ongoing immune process and may thus represent a promising therapy for MS. Recently, 1,25-D3 has been showed to inhibit interleukin-12 production (3), which is known to induce interferon-gamma secretion, which is involved in the inflammatory process during active MS. The aim of the current study was to evaluate the effect of 1-alpha-hydroxy-D3 (Alfacalcidol) the activated form of vitamin D in MS patients, focusing on safety and toxicity. Five patients with definite MS and a relapsing–remitting course were included in the study. Patients were selected to participate if they had a relatively low exacerbation rate not qualifying them to receive accepted relapse preventive treatments. Patients received a detailed explanation, and all provided written informed consent. The study was approved by the ethical committees of the Israeli Ministry of Health. Patients (two women, three men; mean age, 47 years; age range, 45–51 years; mean disease duration, 6.4 years; range of disease duration, 4–12 years; mean EDSS score, 4.5 points; range of EDDS scores, 3.5–5.0 points) were treated with Alfacalcidol at a dosage of 1.5 μg/day for a period of 6 months. Neurologic examination was performed once monthly. Alfacalcidol serum levels were measured at baseline, and at 3 and 6 months. Brain magnetic resonance imaging (2 T, 3-mm slice, no gap; Elscint, Israel) was performed at baseline and on study completion. Throughout the study period patients felt well and no side effects were reported. None of the patients complained of symptoms associated with Alfacalcidol intoxication, and calcium blood levels were within normal range. Neurologic status of patients at the end of the study was as follows: three patients were stable, one patient improved, and one patient had an acute relapse and received treatment with methylprednisolone. The current findings implicate a role for Alfacalcidol in MS. It is possible that in addition to its hormonal effects on neurotransmitter levels and turnover, Alfacalcidol can also regulate myelin basic protein-specific T-helper cells through its effects on interleukin-12 production [8] and thus prevent the inflammatory process during active MS. We suggest that Alfacalcidol is safe and well tolerated by MS patients, and its potential role as an immunomodulating treatment should be investigated in large-scale studies.

Acquired Tracheoesophageal Fistula in Critically Ill Patients

Acquired benign tracheoesophageal fistula (TEF) is an infrequent complication of prolonged intubation and tracheostomy. Not infrequently, it is associated with severe circumferential malacia of the trachea and a need for concomitant correction of both. Controversy exists as to whether this should be performed in a single-stage or a 2-stage procedure. Four patients with acquired TEF underwent operation in a tertiary referral medical center between 1995 and 1997. The operations were performed through either an anterior (3) or a lateral (1) neck approach. Three patients underwent closure of the fistula with tracheal resection and anastomosis in a single stage and are doing well. One patient with complete subglottic stenosis underwent closure of the TEF and was planned for tracheal reconstruction in a second stage. This patient died in the early postoperative period. The complications included aspiration of blood leading to pneumonia (2), spontaneously resolving pneumomediastinum (1), subcutaneous emphysema (2), and cardiac arrhythmia (1). Residual fistula, noted in 1 patient, was treated conservatively and resolved spontaneously within several weeks. We conclude that acquired TEF is amenable to repair through a cervical approach. A single-stage correction of the TEF with reconstruction of the trachea is suitable and successful in most patients. Several stages seem justified when concurrent laryngotracheal reconstruction is needed.

Migration of Fishbone Following Penetration of the Cervical Esophagus Presenting as a Thyroid Mass

Fishbones are among the commonest foreign bodies lodged in the cervical esophagus. A small percentage of them will penetrate the esophageal wall and will be found either intra- or extraluminally. Migration of esophageal foreign bodies to the thyroid gland, and presentation as a mass, is extremely rare. We present such a case and review the relevant literature.

Postoperative spinal epidural empyema : clinical and computed tomography features

Epidural empyema is a rare complication of elective spinal surgery. Four such cases are described. The clinical features of this postoperative complication were surprisingly vague and misleading. Fever was uncommon. Local inflammatory signs or rapid neurologic deterioration were absent. Computerized tomography proved useful in diagnosis and follow-up. Unlike spontaneous spinal epidural abscess, postoperative spinal epidural empyema had a benign course. Causative bacteria were miscellaneous. Surgical evacuation of the purulent collection and appropriate antibiotic therapy resulted in cure in all cases.

Chordoma of the Cervical Spine

INTRODUCTION Chordoma is a slow-growing, localized neoplasm arising from the remains of the embryonic notochord. This is a rare tumor, representing at most 5% of all malignant tumors of bone, and demonstrates a large spectrum of biological behavior. Chordoma may be found in several sites: the sacrococcygeal region, the spheno-occipital region, and the mobile spine. The female-to-male ratio is approximately 1:2.

CT Target Selection in Stereotactic Anterior Capsulotomy: Anatomical Considerations

The first communications concerning stereotactic bilateral anterior capsulotomies were reported by Talairach and Leksell. This procedure has become established for the management of otherwise intractable anxiety neuroses and obsessive compulsive disorders, with a reported success rate of 70% in different series. It has been stressed that results are closely related to the extent of the lesion. The desirable lesion has a tubular shape with a length of 15-18 mm in the coronal axis. This shape is achieved by step withdrawal of a 4- to 5-mm electrode tip along a proper trajectory. A precise angulation of the trajectory is crucial to proceed without lesioning of the adjacent bordering caudate nucleus or putamen in the coronal plane. In the sagittal plane, it has to remain within the limits of the anterior capsula interna and avoid an excessive posteroanterior obliquity to ensure that the entry point through the cortex remains in the prefrontal noneloquent area. To achieve this trajectory, a target 5 mm posterior to the anterior border of the frontal horn, as seen on CT, at the level of the foramen of Monro has been suggested, along with a precoronal burr hole placed 20 degrees from the midline. Following these guidelines we have found the resulting lesions to be excessively anterior, with exclusion of their first 4- to 5-mm deep component. If the same target point is selected at two different axial levels to fix a trajectory, it usually results in an anteriorward trajectory that might require an entry point too close to the motor cortex, because the anterior horn reaches more rostrally as it deepens.(ABSTRACT TRUNCATED AT 250 WORDS)

Upward transtentorial herniation: a complication of postoperative edema at the cervicomedullary junction.

Local edema at the operative bed developed a few hours after uneventful subtotal removal of a lesion occupying the lower medulla and upper cervical cord. The patient experienced apnea, quadriplegia, and circulatory collapse followed by acute respiratory insufficiency. Hydrocephalus secondary to aqueductal occlusion occurred on the 3rd postoperative day. A computerized tomographic scan was compatible with upward transtentorial herniation. The association of this phenomenon with an intra-axial lesion at the cervicomedullary junction has not been previously documented. The pathophysiological mechanisms implicated in this complication are discussed.