Deep endometriosis muscular infiltration of the bowel wall: correlation between MRI and histopathology.

AIM: To assess the correlation between magnetic resonance imaging (MRI) and histopathology for predicting muscular infiltration of endometriosis in the bowel wall in patients undergoing colorectal resection. MATERIALS AND METHODS: All consecutive patients who underwent colorectal surgery for deep endometriosis (DE) with a preoperative MRI in a single tertiary care referral hospital between 2001 and 2019 were included in a prospective cohort. MRI images were revised by a single blinded radiologist. The MRI results regarding the infiltration depth (serosal, muscular, submucosal, or mucosal) and lesion expansion of DE were compared to histopathology. RESULTS: A total of 84 patients were eligible for evaluation. A sensitivity of 89% and positive predictive value of 97% was shown for predicting muscular involvement of the bowel wall. CONCLUSION: This study showed that MRI is valuable in predicting the involvement of the muscular layer of the colorectal wall. Therefore, in patients with symptomatic pelvic bowel endometriosis MRI is a useful tool in guiding the extent of colorectal surgery.

MRI cT1-2 rectal cancer staging accuracy: a population-based study.

BACKGROUND: Adequate MRI-based staging of early rectal cancers is essential for decision-making in an era of organ-conserving treatment approaches. The aim of this population-based study was to determine the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography (ERUS). METHODS: Patients with cT1-2 rectal cancer who underwent local excision or total mesorectal excision (TME) without downsizing (chemo)radiotherapy between 1 January 2011 and 31 December 2018 were selected from the Dutch ColoRectal Audit. The accuracy of imaging was expressed as sensitivity, specificity, and positive predictive value (PPV) and negative predictive value. RESULTS: Of 7382 registered patients with cT1-2 rectal cancer, 5539 were included (5288 MRI alone, 251 MRI and ERUS; 1059 cT1 and 4480 cT2). Among patients with pT1 tumours, 54·7 per cent (792 of 1448) were overstaged by MRI alone, and 31·0 per cent (36 of 116) by MRI and ERUS. Understaging of pT2 disease occurred in 8·2 per cent (197 of 2388) and 27·9 per cent (31 of 111) respectively. MRI alone overstaged pN0 in 17·3 per cent (570 of 3303) and the PPV for assignment of cN0 category was 76·3 per cent (2733 of 3583). Of 834 patients with pT1 N0 disease, potentially suitable for local excision, tumours in 253 patients (30·3 per cent) were staged correctly as cT1 N0, whereas 484 (58·0 per cent) and 97 (11·6 per cent) were overstaged as cT2 N0 and cT1-2 N1 respectively. CONCLUSION: This Dutch population-based analysis of patients who underwent local excision or TME surgery for cT1-2 rectal cancer based on preoperative MRI staging revealed substantial overstaging, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.

ANTECEDENTES: Una adecuada estadificación mediante resonancia magnética nuclear (RMN) de los cánceres de recto en estadios precoces es esencial para la toma de decisiones en una era en la existen diferentes opciones de tratamiento preservadoras del recto. El objetivo de este estudio de base poblacional fue determinar la precisión de la estadificación mediante RMN del cáncer de recto precoz en la práctica diaria, ya sea combinada o no con la ecografía endorectal (endorectal ultrasound, ERUS). MÉTODOS: Los pacientes con cáncer de recto en estadio cT1-2 que se sometieron a resección local o resección total del mesorrecto (total mesorectal excision, TME) sin (quimio) radioterapia neoadyuvante fueron seleccionados a partir del registro auditado ColoRectal holandés, entre el 1 de enero de 2011 y el 31 de diciembre de 2018. La precisión de las imágenes se expresó como sensibilidad, especificidad y valores predictivos positivo y negativo (positive- and negative predicting value, PPV / NPV). RESULTADOS: De un total de 7.382 pacientes registrados con cáncer de recto en estadio cT1-2, se incluyeron 5.539 pacientes (5.288 solamente RMN, 251 RMN + ERUS; 1.059 cT1 y 4.480 cT2). Los pacientes pT1 fueron sobreestadificados cuando se utilizó únicamente la RMN en un 54,7% de los casos (792/1.448) y cuando se combinó RMN y ERUS en un 31,0% (36/116). La infraestadificación de pT2 ocurrió en un 8,2% (197/2.388) y en un 27,9% (31/111), respectivamente. La RMN utilizada como única prueba sobreestadificó los casos pN0 en el 17,3% (570/3.303) y el VPP del estadio cN0 fue del 76,3% (2.733/3.583). De los 834 pacientes con estadio pT1N0, potencialmente adecuado para la resección local, 253 pacientes (30,3%) se clasificaron correctamente como cT1N0, y 484 (58,8%) y 97 (11,6%) pacientes se sobreestadificaron como cT2N0 y cT1-2N1, respectivamente. CONCLUSIÓN: Este estudio de base poblacional holandés en pacientes que se sometieron a una resección local o a cirugía TME por cáncer de recto cT1-2 con estadificación preoperatoria mediante RMN, muestra una considerable sobreestadificación, lo que indica las debilidades y oportunidades en las estrategias de preservación del recto.

Bipolar radiofrequency ablation for symptomatic giant (>10 cm) hepatic cavernous haemangiomas: initial clinical experience.

AIM: To describe initial clinical experience with bipolar radiofrequency ablation (RFA) for symptomatic giant hepatic haemangiomas. MATERIALS AND METHODS: Four consecutive patients with a large-volume, symptomatic hepatic cavernous haemangioma of >10 cm were treated with bipolar RFA during laparotomy with ultrasound guidance. Complications were carefully noted. Clinical and radiological effectiveness were evaluated comparing baseline with 3 and 6 months follow-up of symptom assessments and upper abdominal magnetic resonance imaging (MRI) or computed tomography (CT). RESULTS: RFA was successfully performed for all four giant haemangiomas. No major complications were observed. Peri-procedural shrinking was remarkable and intermediate-term volume reduction ranged from 58-92% after 6 months. Symptom relief after 6 months was complete in two patients and considerable in the other two. CONCLUSION: Preliminary results suggest intra-operative bipolar RFA to be a safe, feasible, and effective technique for treatment of giant symptomatic hepatic cavernous haemangiomas.

Solely inhibin B producing ovarian tumour as a cause of secondary amenorrhoea with hot flushes: case report and review of literature.

In this report, we describe a case of a solely inhibin B producing fibrothecoma presenting with secondary amenorrhoea and hot flushes. Typical laboratory findings were an elevated LH, elevated inhibin B, low FSH and low estrogen. The World Health Organization classification of amenorrhoea was not applicable since the combination of low estrogen and low FSH suggested a central cause, whereas actually there was an ovarian cause. With staging laparotomy, a bilateral borderline tumour was detected in combination with a fibrothecoma. This report underpins the concept of inhibin B being a selective FSH secretion inhibitor of ovarian origin. Furthermore, a literature review on these topics is included.

Advanced image analytics predicting clinical outcomes in patients with colorectal liver metastases: A systematic review of the literature.

BACKGROUND: To better select patients with colorectal liver metastases (CRLM) for an optimal selection of treatment strategy (i.e. local, systemic or combined treatment) new prognostic models are warranted. In the last decade, radiomics has emerged as a field to create predictive models based on imaging features. This systematic review aims to investigate the current state and potential of radiomics to predict clinical outcomes in patients with CRLM. METHODS: A comprehensive literature search was conducted in the electronic databases of PubMed, Embase, and Cochrane Library, according to PRISMA guidelines. Original studies reporting on radiomics predicting clinical outcome in patients diagnosed with CRLM were included. Clinical outcomes were defined as response to systemic treatment, recurrence of disease, and survival (overall, progression-free, disease-free). Primary outcome was the predictive performance of radiomics. A narrative synthesis of the results was made. Methodological quality was assessed using the radiomics quality score. RESULTS: In 11 out of 14 included studies, radiomics was predictive for response to treatment, recurrence of disease, survival, or a combination of outcomes. Combining clinical parameters and radiomic features in multivariate modelling often improved the predictive performance. Different types of individual features were found prognostic. Noticeable were the contrary levels of heterogeneous and homogeneous features in patients with good response. The methodological quality as assessed by the radiomics quality score varied considerably between studies. CONCLUSION: Radiomics appears a promising non-invasive method to predict clinical outcome and improve personalized decision-making in patients with CRLM. However, results were contradictory and difficult to compare. Standardized prospective studies are warranted to establish the added value of radiomics in patients with CRLM.

Magnetic resonance imaging in the evaluation of (deep infiltrating) endometriosis: the value of diffusion-weighted imaging.

PURPOSE: To assess the value of magnetic resonance (MR)diffusion-weighted imaging (DWI) in the evaluation of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: In a prospective single-center study, DWI was added to the standard MRI protocol in 56 consecutive patients with known or suspected endometriosis. Endometriotic lesions as well as (functional) ovarian cysts were analyzed for location, size, and signal intensity on T1, T2, and DWI. Apparent diffusion coefficient (ADC) values were calculated using b-values of 50, 400, 800,and 1200 s/mm(2). Statistical analysis included the Spearman correlation coefficient, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: A total of 110 lesions (62 endometrial cysts and 48 DIE) were detected, 60 of which were large enough to analyze. Mean ADC values of endometrial cysts and functional ovarian cysts were 1.10 x 10(-3)/mm(2)/s and 2.14 x 10(-3)/mm(2)/s, respectively. Mean ADC values of DIE retrocervical, infiltrating the colon, and bladder were 0.70 x 10(-3)/mm(2)/s, 0.77 x 10(-3)/mm(2)/s, and 0.79 x 10(-3)/mm(2)/s, respectively. ADC values of DIE did not show a significant difference between varying pelvic locations (P = 0.63). CONCLUSION: Results of our study suggest that ADC values of DIE are consistently low, without significant difference between pelvic locations.

Magnetic resonance imaging in the evaluation of (deep infiltrating) endometriosis: the value of diffusion-weighted imaging.

PURPOSE: To assess the value of magnetic resonance (MR) diffusion-weighted imaging (DWI) in the evaluation of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: In a prospective single-center study, DWI was added to the standard MRI protocol in 56 consecutive patients with known or suspected endometriosis. Endometriotic lesions as well as (functional) ovarian cysts were analyzed for location, size, and signal intensity on T1, T2, and DWI. Apparent diffusion coefficient (ADC) values were calculated using b-values of 50, 400, 800, and 1200 s/mm(2). Statistical analysis included the Spearman correlation coefficient, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: A total of 112 lesions (62 endometrial cysts and 48 DIE) were detected, 60 of which were large enough to analyze. Mean ADC values of endometrial cysts and functional ovarian cysts were 1.11 x 10(-3)/mm(2)/s and 2.14 x 10(-3)/mm(2)/s, respectively. Mean ADC values of DIE retrocervical, infiltrating the colon, and bladder were 0.70 x 10(-3)/mm(2)/s, 0.79 x 10(-3)/mm(2)/s, and 0.76 x 10(-3)/mm(2)/s, respectively. ADC values of DIE did not show a significant difference between varying pelvic locations (P = 0.63). CONCLUSION: Results of our study suggest that ADC values of DIE are consistently low, without significant difference between pelvic locations.

Surgical outcome and long-term follow-up after segmental colorectal resection in women with a complete obstruction of the rectosigmoid due to endometriosis.

INTRODUCTION: Intestinal involvement is reported in up to 12% of women with endometriosis. Complete large bowel obstruction is a rare complication of intestinal endometriosis. It is estimated to occur in less than 1% of the cases. OBJECTIVE: The aim of this study is to evaluate the surgical outcome and long-term follow-up after segmental colorectal resection in women with a complete obstruction of the rectosigmoid due to endometriosis. In addition, the diagnostic work-up is described and discussed in view of the current literature. PATIENTS AND METHODS: We present a case series of 5 patients with a complete obstruction of the rectosigmoid due to endometriosis who were finally treated in our hospital within a multidisciplinary endometriosis team. We retrospectively analyzed all patients with this condition who were referred in the period January 2000 to December 2006. RESULTS: All patients (mean age 31.8 years, range 25-43 years) underwent emergency surgery resulting in a diverting colostomy before referral to our hospital. The principal diagnostic tool used was magnetic resonance imaging which demonstrated in all patients multiorgan endometriosis with complete obstruction of the rectosigmoid. Thereafter, all patients underwent a segmental colorectal resection by re-laparotomy. The diagnosis intestinal endometriosis was histologically confirmed in all cases. After surgery no major complications occurred. During a follow-up of 18-36 months, residual symptoms such as chronic constipation, deep dyspareunia and chronic pelvic pain were reported in 2 patients. No recurrences of intestinal endometriosis occurred. CONCLUSION: In our case series, segmental colorectal resection showed a favorable surgical outcome with no major complications. In the long-term follow-up, a limited number of residual symptoms were reported and no recurrences occurred. Intestinal endometriosis as a cause of bowel obstruction is often a diagnostic challenge mimicking a broad spectrum of diseases. It should be included in the differential diagnosis in women of reproductive age presenting with any symptoms of bowel obstruction. Magnetic resonance imaging is recommended as the primary imaging technique in such cases. In our opinion, these patients should be treated in a multidisciplinary setting.

Hippocampal sulcus width and cavities: comparison between patients with Alzheimer disease and nondemented elderly subjects.

BACKGROUND AND PURPOSE: The hippocampal fissure is a fetal sulcus that, except for its most medial part (the superficial hippocampal sulcus), is normally obliterated. Hippocampal cavities are residual cysts attributable to lack of hippocampal fissure obliteration. We hypothesized that either hippocampal sulcus enlargement or an increase in number or size of hippocampal cavities could be associated with medial temporal lobe atrophy (MTA) occurring in Alzheimer disease. METHODS: Two observers assessed the maximal hippocampal sulcus width by means of the fimbriosubicular distance at the anterior part of the hippocampal body; as well as the occurrence, number, and size of hippocampal cavities; and the visual rating score of MTA on magnified coronal high-resolution T1-weighted MR images of 21 patients with Alzheimer disease and 15 nondemented elderly controls. RESULTS: Both observers found the maximal hippocampal sulcus width significantly larger in patients with Alzheimer disease than in controls (P < .0001). The interobserver averaged fimbriosubicular distance in patients with Alzheimer disease was 2.84 mm (SD = 0.94), approximately twice that of the corresponding distance in nondemented subjects (1.41 mm; SD, 0.58). Both observers found a significant correlation between the fimbriosubicular distance and MTA score (observer 1, r(s) = 0.71; observer 2, r(s) = 0.74; P < .0001). None of the observers found significant differences between patients with Alzheimer disease and nondemented subjects with respect to occurrence, number, or size of hippocampal cavities, nor did they find a significant correlation between the number or size of hippocampal cavities and MTA. Interobserver agreement ranged from moderate to very good. CONCLUSION: Enlargement of the hippocampal sulcus, assessed by the fimbriosubicular distance, is associated with MTA in Alzheimer disease, but enlargement of the hippocampal cavities is not.

Risk of spontaneous pneumothorax due to air travel and diving in patients with Birt-Hogg-Dubé syndrome.

BACKGROUND AND OBJECTIVES: Birt-Hogg-Dubé syndrome is an autosomal dominant disorder characterized by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal cell cancer due to germline folliculin (FLCN) mutations (Menko et al. in Lancet Oncol 10(12):1199-1206, 2009). The aim of this study was to evaluate the incidence of spontaneous pneumothorax in patients with BHD during or shortly after air travel and diving. METHODS: A questionnaire was sent to a cohort of 190 BHD patients and the medical files of these patients were evaluated. The diagnosis of BHD was confirmed by FLCN mutations analysis in all patients. We assessed how many spontaneous pneumothoraces (SP) occurred within 1 month after air travel or diving. RESULTS: In total 158 (83.2 %) patients returned the completed questionnaire. A total of 145 patients had a history of air travel. Sixty-one of them had a history of SP (42.1 %), with a mean of 2.48 episodes (range 1-10). Twenty-four (35.8 %) patients had a history of pneumothorax on both sides. Thirteen patients developed SP < 1 month after air travel (9.0 %) and two patients developed a SP < 1 month after diving (3.7 %). We found in this population of BHD patients a pneumothorax risk of 0.63 % per flight and a risk of 0.33 % per episode of diving. Symptoms possible related to SP were perceived in 30 patients (20.7 %) after air travel, respectively in ten patients (18.5 %) after diving. CONCLUSION: Based on the results presented in this retrospective study, exposure of BHD patients to considerable changes in atmospheric pressure associated with flying and diving may be related to an increased risk for developing a symptomatic pneumothorax. Symptoms reported during or shortly after flying and diving might be related to the early phase of pneumothorax. An individualized advice should be given, taking also into account patients' preferences and needs.

What is the benefit of treatment with multiple lines of chemotherapy for patients with metastatic breast cancer? A retrospective cohort study.

BACKGROUND: Despite the extensive clinical experience, it is still under debate to what extent patients with metastatic breast cancer (MBC) benefit from multiple lines of chemotherapy beyond standard first or second line treatment. Selection of patients with MBC who will benefit from treatment is crucial to improve outcome and reduce unnecessary toxicity. In this retrospective study, systemic treatment outcome for patients with metastatic MBC is being evaluated. We evaluated to what extent the clinical benefit of prior chemotherapy can predict the success of a subsequent treatment line. METHODS: Ninety-one patients treated with chemotherapy for MBC between January 2005 and January 2009 were included in this study. Clinical characteristics of patients, choices of chemotherapy and response at first evaluation of every treatment line was evaluated based on radiologic and clinical data. RESULTS: Patients received multiple systemic cytotoxic and biological (combination) therapies. 30% of these patients received more than five consecutive systemic (combination) treatments. First line chemotherapy was mostly anthracycline-based, followed by taxanes, capecitabine and vinorelbine. The response rate (RR, complete response plus partial response according to RECIST 1.1) decreased from 20% (95% CI 11-28%) upon first line of treatment to 0% upon the fourth line. The clinical benefit rate (combining RR and stable disease) decreased from 85% (95% CI 78-93%) in the first to 54% (95% CI 26-67) upon the fourth line. 24% of the patients with clinical benefit at first evaluation did not receive a subsequent line of treatment when progressive disease occurred, while sixty-one percent of the patients with progressive disease at first evaluation of a treatment did not receive a subsequent line of chemotherapy. When applied, the efficacy of a subsequent line of treatment was similar for patients independent of previous treatment benefit. CONCLUSION: The clinical benefit at first evaluation from systemic treatment in MBC does not predict for subsequent treatment benefit in this retrospective analysis. The fact that 61% of patients did not receive subsequent treatment after previous treatment failure suggests that either clinical judgement is of critical value in selection of patients to prevent them from unnecessary toxicity or, alternatively indicates that based on the assumption that prior treatment failure predicts for lack of benefit undertreatment of patients occurs. Therefore, a more adequate clinical judgement tool or predictive biomarkers for response are urgently needed to improve treatment outcome.

Development of hypointense lesions on T1-weighted spin-echo magnetic resonance images in multiple sclerosis: relation to inflammatory activity.

OBJECTIVE: To evaluate whether degree of inflammatory activity in multiple sclerosis, expressed by frequency of gadolinium enhancement, has prognostic value for development of hypointense lesions on T1-weighted spin-echo magnetic resonance images, a putative marker of tissue destruction. DESIGN: Cohort design with long-term follow-up. Thirty-eight patients with multiple sclerosis who in the past had been monitored with monthly gadolinium-enhanced magnetic resonance imaging for a median period of 10 months (range, 6-12 months) were reexamined after a median period of 40.5 months (range, 33-80 months). SETTING: Magnetic Resonance Center for Multiple Sclerosis Research, Amsterdam, the Netherlands, referral center. MAIN OUTCOME MEASURES: The new enhancing lesion rate (median number of gadolinium-enhancing lesions per monthly scan) during initial monthly follow-up; hypointense T1 and hyperintense T2 lesion load at first and last visit. RESULTS: The number of enhancing lesions on entry scan correlated with the new enhancing lesions rate (r = 0.64; P<.001, Spearman rank correlation coefficient). The new enhancing lesion rate correlated with yearly increase in T1 (r = 0.42; P<.01, Spearman rank correlation coefficient) and T2 (r = 0.47; P<.01, Spearman rank correlation coefficient) lesion load. Initial T1 lesion load correlated more strongly with yearly increase in T1 lesion load (r = 0.68; P<.01, Spearman rank correlation coefficient). CONCLUSIONS: Degree of inflammatory activity only partially predicted increase in T1 (and T2) lesion load at long-term follow-up. Initial T1 lesion load strongly contributed to subsequent increase in hypointense T1 lesion load, suggesting that there is a subpopulation of patients with multiple sclerosis who are prone to develop destructive lesions.

Magnetization transfer imaging of the spinal cord and the optic nerve in patients with multiple sclerosis.

Magnetization transfer (MT) imaging has been successfully applied to patients with multiple sclerosis (MS), showing lesion heterogeneity, subtle changes in the normal-appearing white matter, and a better correlation with disability, in comparison with conventional magnetic resonance imaging. MT imaging is a fairly simple technique, which allows a quantitative analysis with high spatial resolution to delicate structures like the optic nerve and spinal cord. In the spinal cord, MT imaging can be applied as a contrast augmentation technique. Using the MT ratio (MTR), two studies have reported a mild, but significant, reduction in MT ratio in the cervical spinal cord, compared with healthy controls. In one study, clinical disability correlated independently of cord atrophy with MTR, which may relate to preliminary findings of a correlation between axonal loss and MTR in the spinal cord. In the optic nerve, two studies reported strongly decreased MTR in affected nerves, even in the absence of lesions on conventional imaging; unaffected nerves showed values similar to white matter in the brain. In one study, MTR was significantly correlated with electrophysiological parameters, but not with vision. In conclusion, MT imaging provides a quantifiable parameter that can be applied with high spatial resolution to delicate structures, such as the spinal cord and the optic nerve. Further work is needed to correlate MTR measurements with pathology and, most importantly, with the functional status. Such relationships being established, a quantitative technique such as MTR could be useful in monitoring disease progression in MS.

Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis.

MRI findings are increasingly used as outcome measures in therapeutic trials in MS. The discrepancy between the extent of the lesions on conventional T2 images and the clinical condition of the patient is one of the problems encountered in such studies. This clinical-radiological paradox prevents the use of MRI data as surrogate markers of disability in MS. A recent pilot study suggested a relationship between hypointense lesions on T1 MRI and disability. To assess in more detail the correlation of changes in hypointense lesion load on T1-weighted spin-echo MR images ("black holes") with changes in disability in MS, we studied 46 patients with clinically definite MS at baseline and after a median follow-up of 40 months. There was a significant correlation between baseline disability and hypointense lesion load (Spearman rank correlation coefficient [SRCC] = 0.46, p = 0.001). In secondary progressive patients, the rate of accumulation of these "black holes" was significantly related to progression rate (SRCC = 0.81, p < 0.0001). We speculate that the appearance of hypointense lesions is the MRI equivalent of a failure of remission. Overall, T1 lesion load measurements correlated better with clinical assessments than T2 lesion load measurements. Quantification of hypointense lesion load on T1-weighted spin-echo MRI helps to resolve the clinical-radiological paradox between disability and MRI and has the potential to be a surrogate marker of disability in MS.

Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis.

Postmortem unfixed whole brains from five multiple sclerosis (MS) patients were examined by MRI using a T2- and T1-weighted spin-echo (SE) sequence and histology to investigate the histopathologic characteristics of hypointense lesions on T1-weighted SE MR images. The degree of hypointensity was scored semiquantitatively by two blinded observers in reference to normal-appearing white matter. Signal intensities of the lesions and the normal-appearing white matter were measured to obtain contrast ratios. Hematoxylin-eosin stain was used to assess degree of matrix destruction (decrease of density of the neuropil) and cellularity of a lesion, Klüver-Barrera stain for degree of demyelination, Bodian stain for axonal density, and immunostaining of glial fibrillary acid protein for reactive astrocytes and fibrillary gliosis. Nineteen lesions were selected for analysis. Nearly all lesions were compatible with the chronic MS plaque: hypocellularity, absence of myelinated axons, in the presence of reactive astrocytes. Contrast ratios of the lesions were highly correlated (R = -0.90; p < 0.01), with degree of hypointensity scored semiquantitatively. Degree of hypointensity on T1-weighted SE images did not correlate with degree of demyelination or number of reactive astrocytes, but was associated with axonal density (R = -0.71; p = 0.001). A trend was found with degree of matrix destruction (R = 0.45; p = 0.052). We conclude that, in our limited sample, hypointense lesions seen on T1-weighted SE MR images are associated histopathologically with severe tissue destruction, including axonal loss. Our results need to be substantiated in a larger study on more varied patient material to evaluate the use of hypointense lesions as a surrogate marker of persistent deficit in MS patients.

Improving interobserver variation in reporting gadolinium-enhanced MRI lesions in multiple sclerosis.

Gadolinium-enhanced MRI is a sensitive and objective means to monitor disease activity in multiple sclerosis (MS). We evaluated the interobserver agreement and the value of observer training in reporting enhancing lesions from serial MRI. Scans of 16 MS patients were evaluated by five inexperienced and five experienced observers before and after consensus formation and training. The number of lesions at baseline, and the number of new and persistent lesions at follow-up were scored. For each condition, weighted kappa values (kappa) and the mean average difference to the median (MADM) scores were calculated. Without training, the experienced readers showed good agreement on number of lesions at baseline and new lesions at follow-up, and moderate agreement for persistent lesions. The inexperienced readers showed poor agreement for baseline and persistent lesions, and moderate agreement for new lesions. After training, both groups reported lower absolute numbers of lesions, especially the inexperienced readers. The experienced readers showed good agreement for all lesion types, the inexperienced readers showed agreement for baseline and new lesions, and agreement was moderate for persistent lesions. In both groups MADM scores were < 0.72 for baseline and new lesions, but > 1.2 for persistent lesions. Interobserver agreement is improved by training, especially in inexperienced readers. Interobserver agreement in reporting gadolinium-enhanced lesions is high, which validates the use of serial, enhanced MRI as an outcome parameter in treatment trials in MS.

Interscanner variation in brain MRI lesion load measurements in MS: implications for clinical trials.

We evaluated the effect of interscanner variation on brain MRI-measured lesion volumes and measurement reproducibility in MS. Twenty clinically definite MS patients were each scanned on two or three scanners (a total of 14 scanners were used). In addition, a formalin-fixed MS brain was studied on eight scanners from different manufacturers and with different field strengths. For the formalin-fixed MS brain, on each machine we obtained two scans with slice thicknesses of 5 and 3 mm. Only 5-mm-thick slices were obtained from patients. The lesion volume present on each scan was evaluated three times by a single observer in random order, using a local thresholding technique. In two groups of eight patients scanned on machines with different field strengths, the mean lesion volumes present on scans obtained at 1.5 T were significantly higher than those measured on scans obtained with machines operating at 0.5 and 1.0 T (p < 0.01). When a single observer repeatedly evaluated the same scan, a median introbserver agreement of 98.7% (95% CI, 97.9 to 99.1) was achieved. However, when the observer evaluated the scans from different MRI scanners, the agreement (an interscanner agreement) fell to 91.1% (CI, 90.2 to 94.1). When only scanners operating at 1.5 T were considered, the median interscanner agreement was 96.7% (CI, 95 to 97.5). Also, for the formalin-fixed MS brain, the intraobserver agreements obtained with both slice thicknesses were significantly higher than the corresponding interscanner agreements. The interscanner agreement, but not the intraobserver agreement, obtained with a slice thickness of 3 mm was higher than that obtained with a slice thickness of 5 mm. Our results indicate that lesion volume measurements in MS are influenced significantly by the use of different MR scanners and that a patient included in a serial study should be always scanned with the same MR machine using 3-mm thick slices.

Comparison of two MR sequences for the detection of multiple sclerosis lesions in the spinal cord.

PURPOSE: To compare cardiac-triggered dual-echo spin-echo and magnetization transfer-prepared gradient-echo (MT-GE) MR imaging in the detection of multiple sclerosis (MS) lesions in the spinal cord. METHODS: The cervical spinal cord in 20 patients with MS and in nine healthy volunteers was examined with spin-echo and MT-GE MR imaging. Sagittal images were scored for number of lesions, certainty about lesions, image quality, and visual hindrance by artifacts in random order by two radiologists separately and in a blinded manner. RESULTS: In one healthy volunteer, a lesion was seen on images obtained with both images. Lesion/cord contrast-to-noise ratio was equal on both the MT-GE and T2-weighted spin-echo images. MT-GE images showed better image quality and fewer artifacts than the spin-echo images did. The readers found approximately the same number of lesions. However, the number of definite lesions was higher for the spin-echo sequence than for the MT-GE sequence. One reader found 45 definite lesions with spin-echo and 34 definite lesions with MT-GE. For the other reader, these numbers were 37 (spin-echo) and 31 (MT-GE). On the spin-echo images, 90% of the patients were considered to have definite lesions; on the MT-GE images, the readers found definite lesions in 65% (reader 1) and in 70% (reader 2) of the patients. CONCLUSION: Image quality was better with the MT-GE technique than with the spin-echo technique, and lesion/cord contrast-to-noise ratio on the MT-GE images was equal to that of T2-weighted spin-echo images. However, for detecting spinal cord MS lesions in the sagittal plane, the spin-echo images were preferred to the MT-GE images.

MR of the spinal cord in multiple sclerosis: relation to clinical subtype and disability.

PURPOSE: To determine whether the MR appearance of the spinal cord in patients with multiple sclerosis (MS) differs according to clinical subtype. METHODS: The spinal cords of 20 healthy control subjects and 60 patients with MS (22 with relapsing-remitting disease, 22 with secondary-progressive disease, and 16 with primary-progressive disease) were examined with sagittal dual-echo spin-echo MR imaging and with axial T2*-weighted gradient-echo MR imaging. Two interpreters scored the images for focal lesions and for diffuse abnormalities. Cross-sectional areas of the cords were measured at the C-2 level. RESULTS: No abnormalities were found in any of the control subjects nor in two of the patients. Fifty (83%) of 60 patients had focal lesions. Diffuse abnormality and focal lesions were found in 50% of patients with secondary-progressive MS, in 25% of patients with primary-progressive disease, and in 18% of patients with relapsing-remitting disease. Diffuse abnormality without focal lesions was found in seven patients with primary-progressive MS and in one patient with secondary-progressive MS. Patients with diffuse abnormalities had a smaller cross-sectional area of the spinal cord and they suffered from more disability than did patients without diffuse abnormalities. CONCLUSION: The MR appearance of the spinal cord differs among clinical subgroups of MS. Diffuse abnormality of the spinal cord is associated with a progressive clinical course and greater disability.

Sagittal MR of multiple sclerosis in the spinal cord: fast versus conventional spin-echo imaging.

PURPOSE: We compared conventional spin-echo (CSE) with fast spin-echo (FSE) dual-echo MR images to determine which of these sequences was better able to depict spinal cord abnormalities in patients with multiple sclerosis (MS). METHODS: CSE and FSE dual-echo MR images were obtained in 37 patients with MS and in six healthy control subjects, all of whom were examined on a 1.0-T MR unit with a phased-array coil and cardiac triggering. Two blinded interpreters graded the MR studies, first separately and then by consensus. Images were scored for presence of artifacts, number of focal lesions, and presence of a diffuse increase in signal intensity. RESULTS: No abnormalities were seen in the volunteers. The CSE sequences were significantly less hindered by MR imaging artifacts than were the FSE sequences. Interobserver agreement was slightly higher for the CSE than the FSE sequences. After reaching a consensus, the observers found that both CSE and FSE techniques enabled detection of approximately the same number of focal lesions; however, in three patients, small single lesions seen on the CSE images were missed on the FSE images. Also, depiction of a diffuse increase in signal intensity was better on the CSE images. As a result, more patients had abnormal findings on the CSE sequences than on the FSE sequences (35 versus 31). CONCLUSION: Cardiac-triggered dual-echo FSE sequences are almost as good as CSE sequences for depicting spinal MS lesions. Therefore, in cases of established spinal MS, FSE techniques may be as effective as CSE techniques. Because sensitivity for subtle abnormalities is lower with FSE imaging, CSE remains the preferred technique for patients with suspected MS of the spinal cord.