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.

Implementation of anesthesia quality indicators in Germany : A prospective, national, multicenter quality improvement study.

BACKGROUND: In 2016 the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthetists (BDA) published 10 quality indicators (QI) to compare and improve the quality of anesthesia care in Germany. So far, there is no evidence for the feasibility of implementation of these QI in hospitals. OBJECTIVE: This study tested the hypothesis that the implementation of the 10 QI is feasible in German hospitals. MATERIAL AND METHODS: This prospective three-phase national multicenter quality improvement study was conducted in 15 German hospitals and 1 outpatient anesthesia center from March 2017 to February 2018. The trial consisted of an initial evaluation of pre-existing structures and processes by the heads of the participating anesthesia departments, followed by a 6-month implementation phase of the QI as well as a final re-evaluation phase. The implementation procedure was supported by web-based implementation aids ( www.qi-an.org ) and internal quality management programs. The primary endpoint was the difference in the number of implemented QI per center before and after implementation. Secondary endpoints were the number of newly implemented QI per center, the overall number of successful implementations of each QI, the identification of problems during the implementation as well as the kind of impediments preventing the QI implementation. RESULTS: The average number of implemented QI increased from 5.8 to 6.8 (mean of the differences 1.1 ± 1.3; P < 0.01). Most frequently the QI perioperative morbidity and mortality report (5 centers) and the QI temperature management (4 centers) could be implemented. After the implementation phase, the QI incidence management and patient blood management were implemented in all 16 centers. Implementation of other quality indicators failed mainly due to a lack of time and lack of structural resources. CONCLUSION: In this study the implementation of QI was proven to be mostly feasible in the participating German hospitals. Although several QI could be implemented with minor effort, more time, financial and structural resources would be required for some QI, such as the QI postoperative visit.

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.

[Implementation of anesthesia quality indicators in Germany : A prospective, national, multicenter quality improvement study]. / Implementierung anästhesiologischer Qualitätsindikatoren in Deutschland : Eine prospektive, nationale, multizentrische Qualitätssteigerungsstudie German version.

BACKGROUND: In 2016 the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthetists (BDA) published 10 quality indicators (QI) to compare and improve the quality of anesthesia care in Germany. So far, there is no evidence for the feasibility of implementation of these QI in hospitals. OBJECTIVE: This study tested the hypothesis that the implementation of the 10 QI is feasible in German hospitals. MATERIAL AND METHODS: This prospective three-phase national multicenter quality improvement study was conducted in 15 German hospitals and 1 outpatient anesthesia center from March 2017 to February 2018. The trial consisted of an initial evaluation of pre-existing structures and processes by the heads of the participating anesthesia departments, followed by a 6-month implementation phase of the QI as well as a final re-evaluation phase. The implementation procedure was supported by web-based implementation aids ( www.qi-an.org ) and internal quality management programs. The primary endpoint was the difference in the number of implemented QI per center before and after implementation. Secondary endpoints were the number of newly implemented QI per center, the overall number of successful implementations of each QI, the identification of problems during the implementation as well as the kind of impediments preventing the QI implementation. RESULTS: The average number of implemented QI increased from 5.8 to 6.8 (mean of the differences 1.1 ± 1.3; P < 0.01). Most frequently the QI perioperative morbidity and mortality report (5 centers) and the QI temperature management (4 centers) could be implemented. After the implementation phase, the QI incidence management and patient blood management were implemented in all 16 centers. Implementation of other quality indicators failed mainly due to a lack of time and lack of structural resources. CONCLUSION: In this study the implementation of QI was proven to be mostly feasible in the participating German hospitals. Although several QI could be implemented with minor effort, more time, financial and structural resources would be required for some QI, such as the QI postoperative visit.

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.

Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD. METHODS: In this study we present the clinical data of 115 FLCN mutation carriers from 35 BHD families. RESULTS: Among 14 FLCN mutation carriers who developed renal cancer 7 were <50 years at onset and/or had multifocal/bilateral tumours. Five symptomatic patients developed metastatic disease. Two early-stage cases were diagnosed by surveillance. The majority of tumours showed characteristics of both eosinophilic variants of clear cell and chromophobe carcinoma. The estimated penetrance for renal cancer and pneumothorax was 16% (95% minimal confidence interval: 6-26%) and 29% (95% minimal confidence interval: 9-49%) at 70 years of age, respectively. The most frequent diagnosis in families without identified FLCN mutations was familial multiple discoid fibromas. CONCLUSION: We confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers. The tumours were metastatic in 5 out of 14 patients and tumour histology was not specific for BHD. We found a pneumothorax risk of 29%. We discuss the implications of our findings for diagnosis and management of BHD.

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.

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.