Segmentation of subtraction images for the measurement of lesion change in multiple sclerosis

BACKGROUND AND PURPOSE: Lesion volume change (LVC) assessment is essential in monitoring MS progression. LVC is usually measured by independently segmenting serial MR imaging examinations. Subtraction imaging has been proposed for improved visualization and characterization of lesion change. We compare segmentation of subtraction images (SSEG) with serial single time-point conventional segmentation (CSEG) by assessing the LVC relationship to brain atrophy and disease duration, as well as scan-rescan reproducibility and annual rates of lesion accrual.MATERIALS AND METHODS: Pairs of scans were acquired 1.5 to 4.7 years apart in 21 patients with multiple sclerosis (MS). Scan-rescan MR images were acquired within 30 minutes in 10 patients with MS. LVC was measured with CSEG and SSEG after coregistration and normalization. Coefficient of variation (COV) and Bland-Altman analyses estimated method reproducibility. Spearman rank correlations probed associations between LVC and other measures.RESULTS: Atrophy rate and net LVC were associated for SSEG (R = −0.446; P < .05) but not when using CSEG (R = −0.180; P = .421). Disease duration did not show an association with net lesion volume change per year measured by CSEG (R = −0.360; P = .11) but showed an inverse correlation with SSEG-derived measurements (R = −0.508; P < .05). Scan-rescan COV was lower for SSEG (0.98% ± 1.55%) than for CSEG (8.64% ± 9.91%).CONCLUSION: SSEG unveiled a relationship between T2 LVC and concomitant brain atrophy and demonstrated significantly higher measurement reproducibility. SSEG, a promising tool providing detailed analysis of subtle alterations in lesion size and intensity, may provide critical outcome measures for clinical trials of novel treatments, and may provide further insight into progression patterns in MS.

MR imaging has evolved as a core paraclinical tool for the diagnosis, longitudinal monitoring, and scientific investigation of multiple sclerosis (MS). Subsequent to documenting disease effects at 1 time point, assessing longitudinal change has evolved as the dominant role of MR imaging. In particular, quantification of MR imaging lesion burden has served an important role in the evaluation of MS progression and treatment effects.^1–5 As the expected average annual change in T2 hyperintense lesion volume has been reported to be only 5%–10%,⁶ the sensitivity of quantitative analysis of lesion burden change is paramount. Established methods for evaluating the change in T2 lesions include manual counting of total, new, enlarging, and resolving lesions⁷ and quantitative segmentation of total lesion load at each time point.^8–17Direct segmentation of lesion change based on subtraction of coregistered serial MR images has not yet been extensively studied. This approach promises to be a more robust and sensitive alternative for measuring disease progression on serial MR imaging scans, because it focuses quantification efforts on the subset of lesions showing change, which frequently represent a very small fraction of all lesions.Subtraction imaging, which cancels stable disease, provides enhanced sensitivity to characterize lesions by separately identifying new, enlarging, and resolving MS lesions.^7,18 The segmentation of subtraction images quantifies the new, enlarging, and resolving MS lesions seen on subtraction imaging.In this article, we assessed the sensitivity of 2 image analysis strategies: conventional segmentation followed by the determination of numeric differences between total lesion volumes at each time point (CSEG) versus the segmentation of subtraction images (SSEG). We compared the average yearly change in MS lesion burden using each of these 2 methods and determined measurement precision. By way of external validation, we related the 2 change measures with changes in brain parenchymal fraction (BPF) and disease duration.     

In situ breast carcinoma after treatment during adolescence for thyroid cancer with radioiodine

We reviewed the courses of patients treated during childhood or adolescence for thyroid cancer to estimate the frequency of, and to identify possible risk factors for, the occurrence of second malignant tumors in this population. We identified all patients treated for thyroid cancer in a cohort of 1,406 pediatric cancer patients who were diagnosed prior to 20 years of age during the period January 1, 1960 through December 31, 1988 and who were treated at Roswell Park Cancer Institute. Twelve patients were treated for thyroid cancer, of whom nine were women. In situ breast carcinoma was diagnosed 25 and 26 years after diagnosis of thyroid cancer in two of four women treated with radioiodine. No new cancers were diagnosed in the five women treated with thyroidectomy only. Two of four women treated for thyroid cancer during adolescence with radioiodine, which is concentrated in the breast as well as other organs, developed in situ breast carcinoma. Review of a large cohort of adolescent female thyroid cancer patients treated with radioiodine is necessary to provide an accurate estimate of their risk of developing breast cancer. These patients must remain under medical surveillance throughout their lifetimes to facilitate prompt diagnosis of and early intervention for new conditions, such as the occurrence of breast cancer. © 1995 Wiley-Liss, Inc.     

Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent,selective, melanocortin subtype-4 receptor agonist

Synthetic and natural peptides that act as nonselective melanocortin receptor agonists have been found to be anorexigenic and to stimulate erectile activity. We report the design and development of 1, a potent, selective (1184-fold vs MC3R, 350-fold vs MC5R), small-molecule agonist of the MC4 receptor. Pharmacological testing confirms the food intake lowering effects of MC4R agonism and suggests another role for the receptor in the stimulation of erectile activity.     

Whole-brain atrophy in multiple sclerosis measured by two segmentation processes from various MRI sequences

Recent MRI and pathologic studies have drawn attention to the destructive nature of the multiple sclerosis (MS) disease process, including the early occurrence of axonal and neuronal loss, leading to macroscopic brain and spinal cord atrophy. Measurement of brain atrophy from MRI has emerged as a potential outcome measure and marker of disease severity in MS and neurodegenerative diseases such as Alzheimer's. However, the optimal method for quantifying atrophy has not been established, including the choice of pulse sequence and segmentation algorithm employed. Using two different MRI scanners to ensure generalizability of results, we compared the reproducibility of four pulse sequences and two analysis methods (fully automated [FA] and semi-automated [SA]) when obtaining brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, in patients with MS (n=13) and normal controls (n=2). In order to ensure the validity of our fully automated analysis technique, we also used it to evaluate the atrophy rate over nine months in 57 MS patients from the placebo arm of a clinical trial.All pulse sequences were capable of yielding reproducibility of around 1% coefficient of variation (CoV) or better. The best reproducibility was obtained using 2D multi-slice sequences (conventional spin echo [SE] and fluid-attenuated inversion recovery [FLAIR]), with fully automated analysis. Fully automated analysis of the longitudinal data (conventional spin echo) showed an atrophy rate of -0.5% change in BPF per year, in line with previous findings from a similar cohort of patients.In conclusion, BPF measurement is affected by both pulse sequence and segmentation method. Automated measurement has high reproducibility especially when 2D sequences are used. Semi-automated measurement may have increased accuracy, but with a decreased efficiency and reliability.     

Parent-infant relationship global assessment scale: a study of its predictive validity

The Parent-Infant Relationship Global Assessment Scale (PIRGAS; Zero to Three, 1994) provides a continuously distributed scale of infant-parent relationship adaptation, raging from 'well-adapted' to 'dangerously impaired'. The present study examines the predictive validity of the PIRGAS in a high-risk sample by coding relationship adaptation level from a single sample of 10 min of unstructured free play between mothers and their 20-month-old infants and examining its relationship to subsequent interaction with mothers and behavior problems at 24 months. Relationship adaptation assessed reliably from observations of only 10 min of free play between mothers and their infants at 20 months of age using PIRGAS predicted subsequent mother- infant interaction in a laboratory based problem-solving paradigm (Crowell procedure) at 24 months and internalizing symptomatology of Child Behavior Checklist at age 24 months. These results contribute to the predictive validity of the PIRGAS as a measure of mother-infant relationship adaptation.     

Diffuse magnetic resonance imaging white-matter changes in a 15-year-old boy with mitochondrial encephalomyopathy

We report a 15-year-old boy who presented with recurrent headaches associated with numbness, confusion, and speech difficulty. Brain magnetic resonance imaging (MRI) revealed diffuse bilateral white-matter hyperintensity on fluid-attenuated inversion-recovery and T2-weighted images in the internal capsule, periventricular and subcortical white matter, base of the pons, and middle cerebellar peduncles. Lesions were isointense on T1-weighted images and nonenhancing. Muscle biopsy showed changes consistent with a mitochondrial myopathy. Mitochondrial respiratory chain enzyme activity analysis revealed a significant reduction in complex II activity. Genetic testing was negative. We conclude that mitochondrial encephalomyopathy may present with unusual diffuse supratentorial and infratentorial white-matter changes on MRI.     

Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis

The association between regional measures of cortical atrophy and neuropsychological (NP) dysfunction was studied in 35 multiple sclerosis (MS) patients. Patients underwent neurological examination, MRI, and NP testing. Blind quantitative MRI analysis yielded total T(2) lesion area (TLA) and third ventricle width (3VW). Cortical atrophy, rated by blind visual inspection, was more extensive in superior frontal and parietal cortices than in other regions. No MRI measures were correlated with depression scores. TLA and 3VW were significantly correlated with each NP test. Cortical atrophy measures for bilateral superior frontal cortex were retained in regression models predicting impairments in verbal learning, spatial learning, attention, and conceptual reasoning. The authors conclude that cerebral atrophy predicts NP impairment while accounting for the influence of TLA or 3VW. Regions of cortex most susceptible to atrophic and cognitive changes in MS are the right and left superior frontal lobes.     

Causes of elevated troponin I with a normal coronary angiogram

Abstract
Background : The new definition of myocardial infarction (MI) emphasizes the pre-eminent role of tropo­nin for diagnosis. Troponin rise indicates myocardial injury, but is not synonymous with infarction or ischaemia.
Aims : To review the precipitating event for tropo­nin elevation in patients with angiographically normal coronary arteries, in a district general hospital.
Methods : Consecutive patients with elevated tropo­nin I (TnI) who underwent angiography for suspected coronary disease were included in the present study if they had normal or mild disease (<50% diameter loss without complex features or thrombus). Precipitating event for TnI elevation was assigned on the totality of clinical evidence.
Results : Twenty-one patients qualified, with an average age of 50 years (range 33−73). Sixty-two per cent of participants were female. Troponin release was attributed to tachycardia in six patients, only two of whom had haemodynamic compromise. Physical exertion was the precipitating factor in two patients; pericarditis in two patients; and severe congestive heart failure in one patient. Ten of 21 patients had no identifiable cause for a rise in TnI concentration. Five of 21 patients had left-ventricular wall motion abnormalities. There were no deaths or MI at 41 ± 24 weeks follow up.
Conclusion : Troponin is a sensitive marker of myocardial injury and may rise following apparently minor insults. A rise in TnI concentration may have a cause other than acute coronary syndrome and may occur without significant angiographic coronary artery disease. (Intern Med J 2002; 32: 520−525)