Brain magnetic resonance imaging in adults with asthma.

BACKGROUND: In individuals with asthma, potential central nervous system changes can occur as a consequence of their asthma or therapy. Clinical trials of anti-asthmatic therapies might benefit from using magnetic resonance imaging (MRI) to assess potential brain abnormalities. PURPOSE: As part of the clinical safety evaluation of a monoclonal antibody directed against interleukin-9 for the treatment of asthma, we assessed whether brain MRI is an appropriate screening tool to evaluate potential neurotoxicity. METHODS: Brain MRIs were conducted as part of a prespecified safety evaluation in adults aged 19 to 47 years with mild to moderate asthma treated with either the investigational monoclonal antibody or placebo. An independent neuroradiologist performed a blinded review of brain MRI scans obtained at baseline before dosing and day 28 after dosing from two separate clinical studies. RESULTS: Fifteen brain MRI abnormalities were noted in 13 of 21 subjects with asthma (62%). Nonspecific deep white matter hyperintensities (24%), perivascular space (24%), and abnormal anatomic findings (14%) were noted either at baseline or follow-up. Only 8 of 21 subjects (38%) with asthma had normal brain MRI results. CONCLUSIONS: The high rate of incidental brain MRI findings suggests that these abnormalities are relatively common in patients with asthma. Thus, brain MRI may not be an appropriate screening tool to evaluate potential neurotoxicity in subjects during routine clinical studies without a baseline examination. Due to artifacts simulating lesions, an experienced radiologist should interpret all brain MRI results.

New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate.

BACKGROUND: Hypointense lesions on T1 weighted MRI, referred to as black holes (BH), are a marker of demyelination/axonal loss in multiple sclerosis (MS). There is some evidence that glatiramer acetate (GA) may decrease the conversion of new brain lesions to BH. METHODS: Monthly 3-Tesla brain MRI scans were used for up to 2 years to study the development and evolution of new BH in 75 patients with MS randomised to GA or Interferon beta-1b (IFNbeta1b) in the BECOME study. FINDINGS: Of 1224 newly enhancing lesions (NEL) appearing at baseline through 24 months in 61 patients, 767 (62.7%) showed an acute BH (ABH). The majority of ABH were transient and of similar duration by treatment group. Of 571 ABH in which MRI follow-up scans were available for >or=1 year, 103 (18.8%) were still visible >or=12 months after onset and were considered chronic BH (CBH). Only 12.1% of the 849 NEL with MRI follow-up >or=1 year converted to CBH, 9.8% with IFNbeta1b and 15.2% with GA (p = 0.02). The conversion from ABH to CBH was also lower with IFNbeta1b (15.2%) than with GA (21.4%), of borderline significance (p = 0.06). The majority of patients who developed NEL did not develop CBH; however, about a quarter had conversion rates from ABH to CBH greater than 20%. INTERPRETATION: Only a minority of new brain lesions in patients with MS treated with GA or IFNbeta1b convert to CBH.

Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study.

BACKGROUND: There are no published MRI studies comparing interferon beta 1b (IFNbeta-1b) and glatiramer acetate (GA) for treatment of relapsing multiple sclerosis (MS). OBJECTIVE: To compare the efficacy of IFNbeta-1b and GA for suppression of MS disease activity as evidenced on frequent brain MRI. METHODS: A total of 75 patients with relapsing-remitting MS or clinically isolated syndromes were randomized to standard doses of IFNbeta-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement. The primary outcome was the number of combined active lesions (CAL) per patient per scan during the first year, which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery (FLAIR) lesions. Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years. RESULTS: Baseline characteristics were similar between the groups. The primary outcome showed similar median (75th percentile) CAL per patient per scan for months 1-12, 0.63 (2.76) for IFNbeta-1b, and 0.58 (2.45) for GA (p = 0.58). There were no differences in new lesion or clinical relapses for 2 years. Only 4.4% of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions. CONCLUSION: Patients with relapsing multiple sclerosis randomized to interferon beta 1b or glatiramer acetate showed similar MRI and clinical activity.

Cladribine in aggressive forms of multiple sclerosis.

Cladribine (2-chlorodeoxyadenosine) is an immunosuppressant drug previously evaluated in multiple sclerosis (MS) with variable results. We report six patients with aggressive relapsing MS who despite a poor response to other therapies had a favourable clinical evolution after cladribine. Four women and two men with a rapid increase in the number and severity of relapses leading to increasing disability [mean Expanded Disability Status Scale (EDSS) 6.42, standard deviation +/- 0.58, mean relapse rate per year in the 2 years prior to study entry 2.67 +/- 0.75] were retrospectively evaluated. Brain magnetic resonance imaging (MRI) performed in five patients showed active disease with gadolinium-enhancing lesions. Cladribine was given at 0.07 mg/kg/day for five consecutive days once monthly with a total of 2- to 4-monthly courses. After 6 months, mean EDSS decreased to 3.75 +/- 1.64 and MRIs showed a decrease or suppression in the number of gadolinium-enhancing lesions. After 1 year from first dose, cladribine dosage was repeated in four patients because of recurrence of relapses with subsequent similar positive clinical results. In the follow-up period (49.33 +/- 39.66 months), the mean relapse rate decreased to 0.71 +/- 0.55 and no unexpected or serious adverse events were observed.

Double-shot magnetic resonance imaging of cerebral lesions: fast spin-echo versus echo planar sequences.

The authors compared two new rapid MRI techniques: double-shot echo-planar imaging (DS-EPI) versus double-shot fast spin-echo (DS-FSE) in the evaluation of cerebral lesions. The authors examined 35 patients with 37 lesions, which were hyperintense on long TR images. Patients were scanned with both DS-EPI and DS-FSE with a time of repetition (TR) of 10,000 milliseconds and an echo time (TE) of 80 milliseconds. Conspicuity was determined from region of interest measurements to calculate contrast to noise ratio (C/N). Visual comparisons between DS-EPI and DS-FSE, and between DS-EPI and T2-weighted conventional spin-echo (CSE) were also performed to evaluate the sequences' ability to depict hemorrhage. The mean C/N for both sequences was comparable: 36.7 for DS-FSE and 35.6 for DS-EPI, with no statistically significant difference (p = 0.77). With regards to depicting blood products, DS-EPI proved far more effective than DS-FSE and comparable to CSE. Also, DS-EPI proved to be more time-efficient, requiring 1.67 seconds per section, while DS-FSE required 3.33 seconds per section. Whereas DS-FSE and DS-EPI are comparable in their ability to depict hyperintense cerebral pathology, DS-EPI is more time-efficient, and therefore appears preferable. Because of the high magnetic susceptibility of DS-EPI, geometric distortion degrades visualization of lesions in the posterior fossa or near the sinuses. On the other hand, the high magnetic susceptibility results in high conspicuity of blood products.

Optimization of gray/white matter contrast with fast inversion recovery for myelin suppression: a comparison of fast spin-echo and echo-planar MR imaging sequences.

We compared two MR imaging sequences, fast inversion recovery for myelin suppression (FIRMS) and echo-planar FIRMS (EP-FIRMS), for depicting gray/white matter contrast. In 18 patients, the frequency bandwidth (BW) was optimized for each sequence; in nine patients, the BW was held constant. In the BW-optimized group, the mean contrast-to-noise ratio (C/N) was three times higher with the FIRMS sequence. In the BW-constant group, the mean C/N was 27% higher with the EP-FIRMS sequence; however, geometric distortion degraded the EP-FIRMS images excessively. For optimal gray/white contrast, FIRMS appears to be the superior pulse sequence.

Falcotentorial plasmacytoma. Case report.

Intracranial solitary plasmacytomas are extremely rare tumors and are often misdiagnosed preoperatively. The authors report the successful treatment of a patient who harbored such a tumor involving both the falx and tentorium; this is the second case reported. A 59-year-old woman suffered from a seizure disorder due to a falcotentorial lesion, which had been identified 3 years earlier and was thought at the time to be an en plaque meningioma. Most recently, the patient presented with symptoms of increased intracranial pressure and hemiparesis. Computerized tomography and magnetic resonance imaging of her head revealed progressive growth of the tumor. The patient underwent partial resection of the tumor and chemo- and radiation therapies. Intracranial plasmacytomas must always be included in a differential diagnosis because potential complete cure can be achieved using fairly conservative treatment modalities.

Therapeutic resistance: characterization and inactivation by specific antiserum of a putative protein family produced by tumour cells.

A multitherapy resistance (MTR) factor produced by Cloudman S91 mouse melanoma cells rescues a responsive cell line after gamma-irradiation, short wavelength ultraviolet light, mitomycin C, vinblastine and actinomycin D. A similar activity with respect to ionizing radiation is now shown to be produced by human melanoma cells and by both human and mouse breast cancer cells but not by five normal cell lines. In these studies, the factor produced in serum-free conditioned medium (SFCM) by Cloudman S91/I3 cells is further characterized. Its activity in a clonogenic assay using related Cloudman S91/amel cells is destroyed by trypsin but not by DNase and is stable for at least 8 days at a variety of temperatures including 37 degrees C. Molecules greater than 30 kDa from SFCM collected from S91/I3 cells were concentrated and separated by preparative zonal electrophoresis (PZE). Bioactivity was present in both the cathode- and the anode-running fractions. The active acidic (anode) fractions were analysed by preparative isoelectric focusing. Bioactivity was present between pI 3.5 and 4.2. These PZE fractions were also used to immunize two rabbits, both of which produced antiserum that abrogated the bioactivity of SFCM and of the PZE cathode fractions. Antiserum also decreased the survival of irradiated S91/I3 producer cells that do not respond to SFCM but nonetheless must require MTR proteins for the expression of radiation resistance. These studies present a model for the production of rescue factors by non-clonogenic tumour cells that may persist in some tumours for considerable periods of time.

Single-shot echo-planar imaging of multiple sclerosis: effects of varying echo time.

Our aim was to determine the relative merits of short and long echo times (TE) with single-shot echo-planar imaging for imaging cerebral lesions such as multiple sclerosis. We examined seven patients with clinically definite multiple sclerosis were imaged at 1.5 T. Patients were scanned with spinecho, single-shot echo-planar imaging, using TEs of 45, 75, 105, and 135 ms. Region of interest (ROI) measurements were performed on 36 lesions at or above the level of the corona radiata. The mean image contrast (IC) was highest (231.1) for a TE of 45 ms, followed by 75 ms (218.9), 105 ms (217.9), and 135 ms (191.6). When mean contrast-to-noise ratios (C/N) were compared, the value was again highest (29.7) for TE 45 ms, followed by 75 ms (28.9), 105 ms (28.5), and 135 ms (26.3). In a lesion-by-lesion comparison, TE 45 ms had the highest IC and C/N in the largest number of cases (50 % and 47.2 %, respectively). IC and C/N for TE 45 ms were superior to those of 75 ms in 64% and 58%, respectively. These results support the use of relatively short TEs for single-shot echo-planar imaging in the setting of cerebral lesions such as multiple sclerosis.

Pseudosparing of the endplate: a potential pitfall in using MR imaging to diagnose infectious spondylitis.

OBJECTIVE: The objective of this study was to describe a potential pitfall in using MR imaging to diagnose infectious spondylitis called "pseudosparing" of the endplate, in which the diseased endplate appears to be better defined than a healthy endplate. CONCLUSION: Poor definition of the endplate is a classic radiographic finding in infectious spondylitis; on MR imaging, however, increased conspicuity, or "pseudosparing," was common in our study. Pseudosparing occurs when the normal chemical shift artifact seen in healthy endplates is lost as a result of infiltration of the bone marrow by a pathologic process.

Water-suppression MRI: role in the evaluation of osseous lesions.

The efficacy of chemical shift based water-suppression MRI in the evaluation of bone marrow lesions has not been previously reported. T1-weighted images without and with water suppression were compared in five patients with 16 lesions. There was a significant improvement in the contrast-to-noise ratio (from 4.32 to 5.95, P < 0.01) and contrast ratio (from 1.71 to 5.69, P < 0.004) with water suppression. Water suppression may be useful clinically by increasing the conspicuity of bone marrow lesions.

Encephalocoele as a complication of intranasal sinus surgery: optimal evaluation with magnetic resonance imaging.

We report a case of post-operative frontal basal encephalocoele evaluated using a new magnetic resonance imaging (MRI) sequence, fast inversion recovery for myelin suppression (FIRMS). FIRMS was developed to enhance the differentiation between grey and white matter. In this case, the sequence was beneficial in distinguishing the encephalocoele from adjacent nasal mucosa and secretions.

Gadoteridol in multiple sclerosis patients. A comparison of single and triple dose with immediate vs. delayed imaging.

Enhancement of lesions in multiple sclerosis (MS) has been investigated using standard and high doses of gadolinium. The purposes of this study are to compare the relative merits of single and triple dose as well as examine the merits of delayed triple-dose images in a large group of patients. Thirty-seven patients with multiple sclerosis underwent contrast enhanced brain magnetic resonance imaging (MRI). After noncontrast images, a single dose (0.1 mmol/kg) of gadoteridol was administered. Subsequently, axial T1-weighted images were obtained immediately after administration, and again after a delay of approximately 20 minutes. After an additional 0.2-mmol/kg dose was administered, to provide a total cumulative dose of 0.3 mmol/kg of gadoteridol, immediate and delayed axial T1-weighted image sequences were repeated. The contrast-noise ratio (C/N) was calculated for each identified, enhancing lesion in each series. Furthermore, blinded readings were performed to determine the lesion detection rate. Of the forty definite lesions that underwent all four sequences, triple-dose delayed images exhibited the highest contrast-noise ratio in a significantly larger number of lesions (p < 0.0001). Triple-dose immediate and delayed scans resulted in significantly higher contrast-noise ratios (6.47 and 9.99, respectively) when compared with those of the single dose scans (3.4 for immediate scans and 5.24 for delayed) (p < 0.01). The lesion detection rate was highest for triple dose delayed (95%), followed by triple-dose immediate (83%), single-dose delayed (68%) and finally, single-dose immediate scans (43%). Triple-dose immediate was noted to have a significantly increased (p < 0.0002) lesion detection rate with respect to the standard-dose immediate scans and standard-dose delayed scans (p < 0.02). In four lesions (10% of the total number of lesions), detection occurred only with the triple-dose delayed image sequence. Triple-dose 0.3 mmol/kg gadolinium with delayed imaging resulted in the highest lesion conspicuity and the highest lesion identification rate. There was a trend of progressively increasing detection rates from single-dose immediate scans to triple-dose delayed scans. Triple-dose delayed scans resulted in significantly higher (p < 2 x 10(-8) contrast noise ratios than all other sequences of this study.

Fast inversion recovery for myelin suppression (FIRMS). A new magnetic resonance pulse sequence.

Fast inversion recovery for myelin suppression is a new magnetic resonance sequence with the ability to increase gray-white matter contrast. This can improve the definition of normal anatomical structures.

MRI of pituitary abscess: two cases and review of the literature.

Pituitary abscesses, rare lesions, may be divided into primary and secondary types. Primary pituitary abscesses occur within a previously healthy gland, while secondary abscesses arise within an existing lesion, such as an adenoma, craniopharyngioma, or Rathke's cleft cyst. Secondary abscesses share radiologic characteristics with the lesions from which they arise. There has been no review of the MRI characteristics of primary pituitary abscesses. We report two cases and review the literature. The typical primary pituitary abscess gives the same or slightly lower signal than brain on T1-weighted images, and could be mistaken for a solid mass or presumed to represent a pituitary adenoma. Contrast-enhanced images are useful, demonstrating absence of central enhancement, suggesting a fluid or necrotic center. In one of our cases, meningeal enhancement was obvious; this has not been reported previously and may be diagnostic, when associated with a rim-enhancing pituitary mass.

Optic chiasmal compression by venous aneurysm: magnetic resonance imaging diagnosis.

The overwhelming majority of traumatic carotid cavernous fistulas present with a bruit, arterialization of conjunctival vessels, or an elevated intraocular pressure. Described herein is a patient who presented with progressive deterioration of vision, without any of the above signs. Magnetic resonance imaging demonstrated compression of the optic ch asm by a venous aneurysm arising from a carotid cavernous fistula. This entity should be considered in patients who present with progressive visual loss.

Surgical anatomy of the vertebral arteries.

STUDY DESIGN: This study compared direct measurements of the distances between the vertebral arteries in the cervical spines of human cadaver specimens with data obtained from axial computed tomography images of these specimens. OBJECTIVE: To determine whether the information obtained from a computed tomography scan can be used reliably to predict the true anatomic location of the vertebral arteries and, in so doing, provide accurate guidelines for the lateral extent of anterior cervical decompressive procedures. SUMMARY OF BACKGROUND DATA: Iatrogenic vertebral artery injury during anterior cervical surgery is uncommon, potentially catastrophic, and avoidable. METHODS: The means and standard deviation of measurements of the location of the cervical segment of the vertebral arteries obtained with high-precision, digital calipers by direct gross anatomic dissection of 16 adult (eight male, eight female) cadaver specimens were recorded. These measurements were compared with computed tomography scan data obtained on the same specimens. RESULTS: The mean distances between the vertebral arteries progressively increased from C3 to C6. Computed tomography scan measurements of the distance between the cervical foramina transversaria were consistently smaller than direct measurements of the gross specimens. At C6, the computed tomography scan data were significantly less than the gross anatomic data. CONCLUSIONS: According to these data, computed tomography scan measurements may be used safely and accurately to plan the lateral extent of anterior cervical decompressive surgical procedures. Although the data obtained from the gross anatomic dissections may serve as guidelines to assist the surgeon, the authors recommend a careful review of the preoperative computed tomography scan on an individual case-by-case basis as the safest method to plan for anterior cervical surgery.

Fast inversion recovery for myelin suppression (FIRMS). A new MRI pulse sequence for highlighting cerebral gray matter.

The purpose of this study is to test a new pulse sequence, fast inversion recovery for myelin suppression (FIRMS) for its ability to improve the conspicuity of gray matter. Twenty-six seizure patients were scanned with FIRMS as well as standard sequences. Gray matter conspicuity was evaluated objectively using region-of-interest calculations, including image contrast, contrast ratios, and contrast:noise (C/N). In evaluation of the hippocampus and cortex, all objective measurements of conspicuity were highest for FIRMS. In five clinical cases of suspected cortical dysplasia, FIRMS improved delineation of pathology in positive cases and ruled out the diagnosis in negative cases. In a case of hippocampal sclerosis, FIRMS was able to demonstrate atrophy of the alveus. Fast inversion recovery for myelin suppression holds promise for its ability to highlight the cerebral cortex and hippocampus.

Preoperative MRI diagnosis of Lhermitte-Duclos disease: case report with associated enlarged vessel and syrinx.

BACKGROUND: The most common primary cerebellar tumor is hemangioblastoma, a lesion which is associated with magnetic resonance imaging (MR)-detectable vascularity in over 60%. Lhermitte-Duclos disease is an uncommon cause of a cerebellar mass that is not typically vascular. METHODS: Computed tomography (CT), MRI with and without contrast, and magnetic resonance venography was performed in a patient with a cerebellar mass. RESULTS: The cerebellar mass was noted to have a prominent vessel, as well as an associated syrinx. In spite of MRI-detectable vascularity, the striped appearance of the lesion was felt to be typical of Lhermitte-Duclos disease. At surgery, the mass was resected and the diagnosis of Lhermitte-Duclos disease was confirmed. CONCLUSIONS: The diagnosis of Lhermitte-Duclos disease should be made when MRI shows a parallel linear "tiger-striped" lesion of the cerebellum. The presence of an enlarged vessel and/or syrinx should not deter one from making the preoperative diagnosis.

Giant paraganglioma of the cauda equina in adolescence: magnetic resonance imaging demonstration.

A case of giant paraganglioma of the cauda equina is presented. This is only the second reported case in a minor and the first with magnetic resonance imaging. At 13 cm long, this is the largest paraganglioma of the cauda equina ever recorded.