Quantitative assessment of iron accumulation in the deep gray matter of multiple sclerosis by magnetic field correlation imaging.

BACKGROUND AND PURPOSE: Deposition of iron has been recognized recently as an important factor of pathophysiologic change including neurodegenerative processes in multiple sclerosis (MS). We propose that there is an excess accumulation of iron in the deep gray matter in patients with MS that can be measured with a newly developed quantitative MR technique--magnetic field correlation (MFC) imaging. MATERIALS AND METHODS: With a 3T MR system, we studied 17 patients with relapsing-remitting MS and 14 age-matched healthy control subjects. We acquired MFC imaging using an asymmetric single-shot echo-planar imaging sequence. Regions of interest were selected in both deep gray matter and white matter regions, and the mean MFC values were compared between patients and controls. We also correlated the MFC data with lesion load and neuropsychologic tests in the patients. RESULTS: MFC measured in the deep gray matter in patients with MS was significantly higher than that in the healthy controls (P < or = .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. The increased iron deposition measured with MFC in the deep gray matter in the patients correlated positively with the total number of MS lesions (thalamus: r = 0.61, P = .01; globus pallidus: r = 0.52, P = .02). A moderate but significant correlation between the MFC value in the deep gray matter and the neuropsychologic tests was also found. CONCLUSION: Quantitative measurements of iron content with MFC demonstrate increased accumulation of iron in the deep gray matter in patients with MS, which may be associated with the disrupted iron outflow pathway by lesions. Such abnormal accumulation of iron may contribute to neuropsychologic impairment and have implications for neurodegenerative processes in MS.

Diffusion tensor imaging in multiple sclerosis: assessment of regional differences in the axial plane within normal-appearing cervical spinal cord.

BACKGROUND AND PURPOSE: Evaluation of the spinal cord is important in the diagnosis and follow-up of patients with multiple sclerosis. Our purpose was to investigate diffusion tensor imaging (DTI) changes in different regions of normal-appearing spinal cord (NASC) in relapsing-remitting multiple sclerosis (RRMS). METHODS: Axial DTI of the cervical spinal cord was performed in 24 patients with RRMS and 24 age- and sex-matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated in separate regions of interest (ROIs) in the anterior, lateral, and posterior spinal cord, bilaterally, and the central spinal cord, at the C2-C3 level. Patients and control subjects were compared with respect to FA and MD with the use of an exact Mann-Whitney test. Logistic regression and receiver operating characteristic (ROC) curve analysis assessed the utility of each measure for the diagnosis of RRMS. RESULTS: DTI metrics in areas of NASC in MS were significantly different in patients compared with control subjects; FA was lower in the lateral (mean +/- SD of 0.56 +/- 0.10 versus 0.69 +/- 0.09 in control subjects, P < .0001), posterior (0.52 +/- 0.11 versus 0.63 +/- 0.10, P < .0001), and central (0.53 +/- 0.10 versus 0.58 +/- 0.10, P = .049) NASC ROIs. Assessing DTI metrics in the diagnosis of MS, a sensitivity of 87.0% (95% confidence interval [CI], 66.4 to 97.1) and a specificity of 91.7% (95% CI, 73.0 to 98.7) were demonstrated. CONCLUSION: The NASC in RRMS demonstrates DTI changes. This may prove useful in detecting occult spinal cord pathology, predicting clinical course, and monitoring disease progression and therapeutic effect in MS.

The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Advancements in imaging technologies and newly evolving treatments offer the promise of more effective management strategies for MS. Until recently, confirmation of the diagnosis of MS has generally required the demonstration of clinical activity that is disseminated in both time and space. Nevertheless, with the advent of MRI techniques, occult disease activity can be demonstrated in 50 to 80% of patients at the time of the first clinical presentation. Prospective studies have shown that the presence of such lesions predicts future conversion to clinically definite (CD) MS. Indeed, in a young to middle-aged adult with a clinically isolated syndrome (CIS), once alternative diagnoses are excluded at baseline, the finding of three or more white matter lesions on a T2-weighted MRI scan (especially if one of these lesions is located in the periventricular region) is a very sensitive predictor (>80%) of the subsequent development of CDMS within the next 7 to 10 years. Moreover, the presence of two or more gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new Gd enhancement on follow-up scans are also highly predictive of the subsequent development of CDMS in the near term. By contrast, normal results on MRI at the time of clinical presentation makes the future development of CDMS considerably less likely.

The costs of CT procedures in an academic radiology department determined by an activity-based costing (ABC) method.

PURPOSE: The purpose of this work was to determine the costs of computed tomography (CT) procedures in a large academic radiology department, including both professional (PC) and technical (TC) components, by analyzing actual resource consumption using an activity-based costing (ABC) method and comparing them with Medicare payments. METHOD: Over a 12 month period from July 1, 1996, to June 30, 1997, 1,011 CT procedures, representing 16 Physicians' Current Procedural Terminology (CPT) codes and 98.3% of CT studies performed, were carefully observed by a research assistant trained in ABC methodology. Information collected during these time and motion studies included personnel/machine time and direct materials used. Actual resource units used during the different activities in each CT procedure were valued using appropriate cost drivers. Unit values for both direct and overhead costs were calculated: the cost of an individual procedure equaled the sum of component costs. Costs were compared with PC and TC payments according to the 1997 Medicare Fee Schedule. RESULTS: Total costs of CPT codes 70450 (CT Head unenhanced), 71260 (CT Chest enhanced), and 74160 (CT Abdomen enhanced), which represented 71.2% of CT studies performed, were $189.19, $273.53, and $343.20, respectively. For all 16 nonmodified CPT codes analyzed, Medicare's professional reimbursement was less than the professional cost, whereas its technical reimbursement exceeded respective cost in 14 of the 16 codes. CONCLUSION: In the setting and time period studied, Medicare underreimbursed professional costs while overreimbursing technical costs.

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.

OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS.

Assessment of spinal cord damage in MS using MRI.

Spinal cord imaging is important in the evaluation of patients with MS. There are several techniques available which provide satisfactory images of lesions in the spinal cord. Conventional measures used in the assessment of damage to the spinal cord include quantification of: (1) high intensity on T2 weighted images; (2) spinal cord enhancement; and (3) spinal cord atrophy. Although not presently implemented, newer methods including magnetization transfer, diffusion, and proton spectroscopy offer the potential for more specific classification of spinal cord MS. Assessment of spinal cord damage using MR still remains behind the development of brain methodology and represents both a challenge and an opportunity.

Assessment of posterior fossa damage in MS using MRI.

In multiple sclerosis (MS), brain stem and cerebellum are frequent sites of damage in clinically isolated syndromes at presentation and it is likely that lesions located in such structures can have an important impact on the development of disability in the definite forms of the disease. In patients presented with isolated brain stem syndromes, the symptomatic lesion was often not detected by magnetic resonance (MR) imaging. But patients with asymptomatic infratentorial lesions progressed to clinically definite MS in 65% of cases. Infratentorial lesions are included in various MR criteria designed to assist in the differential diagnosis of MS lesions from incidental lesions, to differentiate MS from subcortical encephalopathic arteriopathy. The preferred MR sequence to visualize infratentorial lesions is the fast spin echo sequence. It is preferred to conventional spin echo and fast fluid attenuated inversion recovery sequences because of its relatively short acquisition time and good sensitivity. The correlation between disability and infratentorial lesion load on T2 weighted sequences is controversial. However, it was recently shown that the correlations between clinical measures and T1 lesion load, histogram magnetization transfer ratio and peak positions, and infratentorial volume measurements are strong. These findings suggest that one of the major factors in the development of disability in patients with MS is the pathological damage in clinically eloquent sites such as the brain stem and cerebellum.

Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals.

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS.

Clinical assessment of MR of the brain in nonsurgical inpatients.

PURPOSE: To evaluate the effect of MR imaging of the brain on four domains of patient care: diagnosis, diagnostic workup, therapy, and prognosis. METHODS: Pre- and post-MR written questionnaires and oral interviews were administered to the referring clinicians of 103 medical and neurologic inpatients at a tertiary care institution. Additional information was obtained from radiologic reports and records. RESULTS: The study population had a diverse array of signs and symptoms and of presumptive clinical diagnoses, reflecting the breadth of disease seen at our institution. The vast majority of physicians (89%) reported that MR imaging added significant diagnostic information, playing an important role in guiding diagnostic workup (24%), planning treatment (34%), and estimating prognosis (47%). MR imaging was significantly more likely to decrease than to increase confidence in the presumptive clinical diagnosis. Thus, MR imaging may be most useful in the setting of diagnostic uncertainty. CONCLUSION: Our results show that MR imaging of the brain has important effects on each of the four domains of care for medical inpatients.

Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements.

PURPOSE: To assess for the presence of microscopic abnormalities in otherwise normal-appearing white matter on T2-weighted images in patients with multiple sclerosis (MS) by using magnetization-transfer (MT) measurements. MATERIALS AND METHODS: Twenty-three patients with MS and nine healthy control subjects underwent magnetic resonance (MR) imaging with a 1.5-T system. MT ratios (MTRs) were measured in 16 areas of normal-appearing white matter identified on conventional T2-weighted images in patients with MS. MTRs in the same white-matter locations in control subjects were determined. The two groups were compared. RESULTS: The mean whole-brain MTR of normal-appearing white matter in patients was 40.13% +/- 1.37 (standard deviation; range, 36.31%-42.09%); in control subjects, 42.93% +/- 0.95 (range, 41.62%-44.50%). The difference was statistically significant (P < or = .001). Except for the internal capsules, the difference in mean MTRs in each sublocation of the brain between patients and control subjects was statistically significant (P < or = .05). CONCLUSION: MT measurements are more sensitive than conventional MR imaging in the detection of abnormalities beyond the resolution of T2-weighted imaging.

Penetrating neck trauma: sensitivity of clinical examination and cost-effectiveness of angiography.

PURPOSE: To evaluate penetrating neck trauma for (a) sensitivity of the clinical examination as an indicator of clinically significant vascular injury, and (b) cost-effectiveness of performing screening diagnostic angiography. METHODS: The medical records of all patients with penetrating neck trauma presenting at our institution over 4 years were retrospectively reviewed. Injuries were classified into one of three anatomic zones and classified into four mutually exclusive groups based on the extent of vascular injury; (a) no vascular injury; (b) minor vascular abnormality; (c) major vascular abnormality without a change in clinical management; or (d) any injury requiring a change in clinical management. Cost data were also obtained for each patient's hospitalization. RESULTS: There were 111 patients with penetrating neck trauma. No statistically significant difference between the sensitivities of the clinical examination or angiography for the detection of vascular injury were detected. Of the 48 patients who had vascular injuries, 45 had an abnormal clinical findings (93.7% sensitivity). None of the remaining 3 patients with vascular injury and normal clinical findings would have had their treatment altered by the results of angiography. The calculated cost of using angiography as a screening tool for vascular injury in patients with normal clinical findings was approximately $3.08 million per central nervous system event prevented. CONCLUSION: Our study suggests that in patients with zone II penetrating neck injuries the clinical examination is sufficient to detect significant vascular lesions and that screening angiography may not be indicated. Because our sample size was relatively small and the mean follow-up only 13.3 days, further investigation is needed to demonstrate definitively the lack of usefulness of screening angiography.