G. Lutterbey

Distinct neuromuscular phenotypes in myotonic dystrophy types 1 and 2 : A whole body highfield MRI study

AbstractMyotonic Dystrophy Type 1 (DM1) and 2 (DM2) present with distinct though overlapping clinical phenotypes. Comparative imaging data on skeletal muscle involvement are not at present available. We used the novel technique of whole body 3.0 Tesla (T) Magnetic Resonance Imaging (MRI) to further characterize musculoskeletal features in DM2 and compared the results with DM1.MRI findings of 15 DM1 and 14 DM2 patients were evaluated with respect to patterns of skeletal muscle affection and clinical data using the Muscular Impairment Rating Scale (MIRS) and Medical Research Council scale (MRC).All DM1 patients had pathological MRI compared with only 5 DM2 patients. In contrast to DM2, DM1 patients showed a characteristic distribution of muscle involvement with frequent and early degeneration of the medial heads of gastrocnemius muscles, and a perifemoral semilunar pattern of quadriceps muscle affection sparing the rectus femoris. The most frequently affected muscles in DM1 were the medial heads of gastrocnemius, soleus, and vastus medialis muscles. In DM2, however, the erector spinae and gluteus maximus muscles were most vulnerable to degeneration. MRI data were in line with the clinical grading in 12 DM1 and 3 DM2 patients. In 3 DM1 and 5 DM2 patients, MRI detected subclinical muscle involvement. 9 DM2 patients with mild to moderate proximal muscle weakness and/or myalgias had normal MRI. Pathological MRI changes in DM2 emerged with increasing age and were restricted to women.Whole body 3.0T MRI is a sensitive imaging technique that demonstrated a characteristic skeletal muscle affection in DM1. In contrast, MRI was no reliable indicator for skeletal muscle involvement in mildly affected DM2 patients since myalgia and mild paresis were usually not reflected by MRI signal alterations.

Distinct neuromuscular phenotypes in myotonic dystrophy types 1 and 2

AbstractMyotonic Dystrophy Type 1 (DM1) and 2 (DM2) present with distinct though overlapping clinical phenotypes. Comparative imaging data on skeletal muscle involvement are not at present available. We used the novel technique of whole body 3.0 Tesla (T) Magnetic Resonance Imaging (MRI) to further characterize musculoskeletal features in DM2 and compared the results with DM1.MRI findings of 15 DM1 and 14 DM2 patients were evaluated with respect to patterns of skeletal muscle affection and clinical data using the Muscular Impairment Rating Scale (MIRS) and Medical Research Council scale (MRC).All DM1 patients had pathological MRI compared with only 5 DM2 patients. In contrast to DM2, DM1 patients showed a characteristic distribution of muscle involvement with frequent and early degeneration of the medial heads of gastrocnemius muscles, and a perifemoral semilunar pattern of quadriceps muscle affection sparing the rectus femoris. The most frequently affected muscles in DM1 were the medial heads of gastrocnemius, soleus, and vastus medialis muscles. In DM2, however, the erector spinae and gluteus maximus muscles were most vulnerable to degeneration. MRI data were in line with the clinical grading in 12 DM1 and 3 DM2 patients. In 3 DM1 and 5 DM2 patients, MRI detected subclinical muscle involvement. 9 DM2 patients with mild to moderate proximal muscle weakness and/or myalgias had normal MRI. Pathological MRI changes in DM2 emerged with increasing age and were restricted to women.Whole body 3.0T MRI is a sensitive imaging technique that demonstrated a characteristic skeletal muscle affection in DM1. In contrast, MRI was no reliable indicator for skeletal muscle involvement in mildly affected DM2 patients since myalgia and mild paresis were usually not reflected by MRI signal alterations.

Does high field MRI allow an earlier diagnosis of multiple sclerosis

BackgroundHigh field magnetic resonance imaging (MRI) provides higher lesion load measurements in patients presenting with clinically isolated syndromes (CIS) suggestive of demyelination and has impact upon the classification of these syndromes and potentially, the diagnosis of multiple sclerosis (MS).PurposeTo investigate whether high field MRI can provide an earlier diagnosis of definite MS within the International Panel (IP) and Swanton criteria.MethodsForty patients presenting with CIS suggestive of MS were included. All patients received multi-sequence MRI at 1.5 Tesla (T) and 3T as well as a neurological assessment at baseline. Follow-up visits including MRI at both field strengths and neurological examinations were scheduled 3–4 and 6–7 months after the first clinical event. Based on MRI and clinical findings, fulfilled IP criteria as well as Swanton criteria were analysed.ResultsAt baseline, the higher detection rate of inflammatory lesions using high field MRI leads to higher classifications according to the Swanton criteria in 15 % of the patients. One additional patient was diagnosed with dissemination in space according to Swanton and IP criteria. During follow-up, an earlier diagnosis of definite MS could not be accomplished, neither according to the IP nor to the Swanton criteria.ConclusionAlthough high field MRI shows a higher detection rate of inflammatory brain lesion in CIS and MS patients with an influence according to MRI criteria, this influence does not lead to an earlier diagnosis of lesion dissemination in time and therefore definite MS.

High field MR imaging and 1H-MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis : Correlation between metabolic alterations and diagnostic MR imaging criteria

PurposeTo prospectively investigate metabolic changes in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) and to correlate these changes to conventional MR imaging findings in terms of MR imaging criteria. Materials and methodsMultisequence MR imaging of the brain and 1H-MR spectroscopy of the parietal NAWM were performed in 31 patients presenting with CIS and in 20 controls using a 3. 0 T MR system. MR imaging criteria and International Panel criteria were assessed based on imaging, clinical and paraclinical results. Metabolite ratios and absolute concentrations of N-acetyl-aspartate (tNAA), myoinositol (Ins), choline (Cho), and total creatine (tCr) were determined. The metabolite concentrations were correlated with the fulfilled MR imaging criteria.ResultsIn comparison to the control group, the CIS group showed significantly decreased mean tNAA concentrations (–8. 1%, p = 0. 012). Significant changes could not be detected regarding Ins, tCr and Cho. No significant correlations between absolute metabolite concentrations and MR imaging criteria were observed. Patients with and without a lesion dissemination in space showed no significant differences of their metabolite concentrations.ConclusionAs assessed by 1H-MRS a significant axonal damage already occurs during the first demyelinating episode in patients with CIS. Conventional MR imaging in terms of diagnostic imaging criteria does not significantly reflect NAWM disease activity in terms of metabolic alterations detected by 1H-MR spectroscopy.

Magnetic resonance spectroscopic and relaxometric determination of bone marrow changes in anorexia nervosa.

Objective The objective of this study was to assess and quantify bone marrow changes in patients with anorexia nervosa using 1H magnetic resonance spectroscopy and relaxometry. Methods The bone marrow fat fraction and the longitudinal and transverse relaxation times (T1 and T2, respectively) of water were measured in the lumbar and femoral marrow of 20 patients with anorexia nervosa and 19 healthy control subjects. Results Patients with anorexia nervosa showed significant hyperhydration and reduction of the fat fraction in their bone marrow, predominantly in the proximal femur. These changes were associated with hematological abnormalities. In a retest of seven patients after psychotherapy and gain of weight, the pathological changes in marrow proved to be largely reversible in correlation with the increase in body mass index. Conclusions Fat depletion and excess of tissue water in the bone marrow in anorexia nervosa can be quantified by 1H magnetic resonance spectroscopy and relaxometry. The distribution of the pathological changes in the lumbar and femoral marrow follows the pattern of normal bone marrow conversion from hematopoietic to cellular during childhood.

Different early pathogenesis in myotilinopathy compared to primary desminopathy.

Mutations in the human myotilin gene may cause limb-girdle muscular dystrophy 1A and myofibrillar myopathy. Here, we describe a German patient with the clinically distinct disease phenotype of late adult onset distal anterior leg myopathy caused by a heterozygous S55F myotilin mutation. In addition to a thorough morphological and clinical analysis, we performed for the first time a protein chemical analysis and transient transfections. Morphological analysis revealed an inclusion body myopathy with myotilin- and desmin-positive aggregates. The clinical and pathological phenotype considerably overlaps with late onset distal anterior leg myopathy of the Markesbery-Griggs type. Interestingly, all three analyzed myotilin missense mutations (S55F, S60F and S60C) do not lead to gross changes in the total amount of myotilin or to aberrant posttranslational modifications in diseased muscle, as observed in a number of muscular dystrophies. Transiently transfected wild-type and S55F mutant myotilin similarly colocalised with actin-containing stress fibers in BHK-21 cells. Like the wild-type protein, mutated myotilin did not disrupt the endogenous desmin cytoskeleton or lead to pathological protein aggregation in these cells. This lack of an obvious dominant negative effect sharply contrasts to transfections with, for instance, the disease-causing A357P desmin mutant. In conclusion our data indicate that the disorganization of the extrasarcomeric cytoskeleton and the presence of desmin-positive aggregates are in fact late secondary events in the pathogenesis of primary myotilinopathies, rather than directly related. These findings suggest that unrelated molecular pathways may result in seemingly similar disease phenotypes at late disease stages.

Volumetric changes of the breast during radiotherapy. Is a replanning necessary for the electron boost

Hintergrund und Ziel:Eine Radiotherapie der Mamma induziert eine Gewebereaktion mit daraus resultierendem Ödem. Dieses Ödem führt zu einer Volumenzunahme der Mamma. Ziel der Studie war es, diese Volumenzunahme zu quantifizieren und deren Einfluss auf die Planung des Elektronenboosts zu analysieren.Patienten und Methodik:Bei 140 Patientinnen mit Mammakarzinom nach brusterhaltender Therapie erfolgte vor, während und/oder nach der Bestrahlung eine CT-Planung, um die Volumenveränderungen während der Bestrahlung zu evaluieren. Die ermittelten CT-Daten wurden unter Verwendung des HELAX-TMS-Planungssystems zur Bestimmung der Dosisverteilung ausgewertet. Die Bestimmung des Brustvolumens erfolgte mittels Interpolationsalgorithmus. Gemessen am Ausgangsvolumen wurden die Patientinnen in drei Subgruppen unterteilt: Gruppe 1 (n = 47): ≤ 670 cm3, Gruppe 2 (n = 46): 671–999 cm3 und Gruppe 3 (n = 47): ≥ 1 000 cm3 Brustvolumen.Ergebnisse:Initial zeigte sich ein mittleres Brustvolumen von 907 cm3 (100–3 073 cm3). Nach Radiotherapie kam es zu einem Anstieg des Brustvolumens um durchschnittlich 81 cm3 auf 988 cm3 (109–3 185 cm3). Signifikant messbare Volumenzunahmen traten ab einer Zielvolumendosis von 40 Gy auf. Bezogen auf die drei Subgruppen ergaben sich folgende mittlere Volumenzunahmen: Gruppe 1: 53 cm3 (3–120 cm3), Gruppe 2: 85 cm3 (20–200 cm3) und Gruppe 3: 105 cm3 (5–340 cm3). Der Zuwachs war in allen drei Gruppen mit einem p-Wert von p < 0,001 hochsignifikant. Je nach Volumenzunahme der Brust resultierte eine Änderung der Herdtiefe um bis zu 1,0 cm.Schlussfolgerung:Aufgrund der interkurrenten Volumenänderungen unter Bestrahlung erscheint eine zweite CT-Untersuchung zur Nachplanung vor Boostbestrahlung sinnvoll. Die zweite CT-Planung sollte ab 40 Gy erfolgen, um das Ödem ausreichend erfassen zu können.Background and Purpose:Radiotherapy can induce tissue reactions with an edema leading to increased breast volume. The aim of the present study was to quantify this increase and analyze its effect on the electron boost technique.Patients and Methods:140 patients with breast cancer treated with breast-conserving surgery underwent CT planning before, during and/or after radiotherapy in order to evaluate breast volume changes due to radiotherapy. CT data were analyzed using the HELAX planning system and dose distribution was assessed. Determination of the breast volume was achieved using an interpolation algorithm. Three subgroups were analyzed: group 1 (n = 47): ≤ 670 cm3, group 2 (n = 46): 671–999 cm3, and group 3 (n = 47): ≥ 1000 cm3 breast volume.Results:The mean initial breast volume was 907 cm3 (100–3073 cm3). After radiotherapy, mean breast volume increased by 81 cm3 to 988 cm3 (109–3185 cm3). Significant changes in volume were observed after a dose of 40 Gy. According to the subgroups mean volume increase was as follows: group 1: 53 cm3 (3–120 cm3), group 2: 85 cm3 (20–200 cm3), and group 3: 105 cm3 (5–340 cm3). This difference was statistically significant for all subgroups (p < 0.001). Corresponding to the volume increase, depth of the boost target volume changed up to 1.0 cm.Conclusion:As radiotherapy may lead to a significant increase in breast volume, it seems appropriate to perform a second planning CT after about 40 Gy in order to optimize dose distribution for boost irradiation.

Volumetrische Veränderungen der Mamma während der Radiotherapie

Hintergrund und Ziel:Eine Radiotherapie der Mamma induziert eine Gewebereaktion mit daraus resultierendem Ödem. Dieses Ödem führt zu einer Volumenzunahme der Mamma. Ziel der Studie war es, diese Volumenzunahme zu quantifizieren und deren Einfluss auf die Planung des Elektronenboosts zu analysieren.Patienten und Methodik:Bei 140 Patientinnen mit Mammakarzinom nach brusterhaltender Therapie erfolgte vor, während und/oder nach der Bestrahlung eine CT-Planung, um die Volumenveränderungen während der Bestrahlung zu evaluieren. Die ermittelten CT-Daten wurden unter Verwendung des HELAX-TMS-Planungssystems zur Bestimmung der Dosisverteilung ausgewertet. Die Bestimmung des Brustvolumens erfolgte mittels Interpolationsalgorithmus. Gemessen am Ausgangsvolumen wurden die Patientinnen in drei Subgruppen unterteilt: Gruppe 1 (n = 47): ≤ 670 cm3, Gruppe 2 (n = 46): 671–999 cm3 und Gruppe 3 (n = 47): ≥ 1 000 cm3 Brustvolumen.Ergebnisse:Initial zeigte sich ein mittleres Brustvolumen von 907 cm3 (100–3 073 cm3). Nach Radiotherapie kam es zu einem Anstieg des Brustvolumens um durchschnittlich 81 cm3 auf 988 cm3 (109–3 185 cm3). Signifikant messbare Volumenzunahmen traten ab einer Zielvolumendosis von 40 Gy auf. Bezogen auf die drei Subgruppen ergaben sich folgende mittlere Volumenzunahmen: Gruppe 1: 53 cm3 (3–120 cm3), Gruppe 2: 85 cm3 (20–200 cm3) und Gruppe 3: 105 cm3 (5–340 cm3). Der Zuwachs war in allen drei Gruppen mit einem p-Wert von p < 0,001 hochsignifikant. Je nach Volumenzunahme der Brust resultierte eine Änderung der Herdtiefe um bis zu 1,0 cm.Schlussfolgerung:Aufgrund der interkurrenten Volumenänderungen unter Bestrahlung erscheint eine zweite CT-Untersuchung zur Nachplanung vor Boostbestrahlung sinnvoll. Die zweite CT-Planung sollte ab 40 Gy erfolgen, um das Ödem ausreichend erfassen zu können.Background and Purpose:Radiotherapy can induce tissue reactions with an edema leading to increased breast volume. The aim of the present study was to quantify this increase and analyze its effect on the electron boost technique.Patients and Methods:140 patients with breast cancer treated with breast-conserving surgery underwent CT planning before, during and/or after radiotherapy in order to evaluate breast volume changes due to radiotherapy. CT data were analyzed using the HELAX planning system and dose distribution was assessed. Determination of the breast volume was achieved using an interpolation algorithm. Three subgroups were analyzed: group 1 (n = 47): ≤ 670 cm3, group 2 (n = 46): 671–999 cm3, and group 3 (n = 47): ≥ 1000 cm3 breast volume.Results:The mean initial breast volume was 907 cm3 (100–3073 cm3). After radiotherapy, mean breast volume increased by 81 cm3 to 988 cm3 (109–3185 cm3). Significant changes in volume were observed after a dose of 40 Gy. According to the subgroups mean volume increase was as follows: group 1: 53 cm3 (3–120 cm3), group 2: 85 cm3 (20–200 cm3), and group 3: 105 cm3 (5–340 cm3). This difference was statistically significant for all subgroups (p < 0.001). Corresponding to the volume increase, depth of the boost target volume changed up to 1.0 cm.Conclusion:As radiotherapy may lead to a significant increase in breast volume, it seems appropriate to perform a second planning CT after about 40 Gy in order to optimize dose distribution for boost irradiation.

Modulation des Refokussierungswinkels in TSE Sequenzen mit FAS (Flip Angle Sweep).

Ziele: Die Verwendung von TSE (FSE) -Sequenzen mit zahlreichen 180° Refokussierungspulsen ist bei 3T durch die SAR Begrenzungen limitiert. Eine Erniedrigung der SAR ist unter anderem durch eine Reduzierung des Refokussierungwinkels wahrend eines Echozuges moglich (Hyperecho/FAS). Diese Studie untersucht den Einfluss der FAS-Technik (Flip Angle Sweep) auf den Bildkontrast bei Leberuntersuchungen. Methode: 7 Probanden wurden an einem 3T System (Intera, Philips MS, Best NL) unter Verwendung einer Oberflachenspule (Syn-cardiac) untersucht. Es wurden atemgetriggerte T2 gewichtete TSE Sequenzen (TR/TE: >4000/80ms, SD/Matrix: 8mm/256, ETL: 18) mit unterschiedlichen FAS-Winkeln (ohne FAS, 150°, 120°, 90°, 75°, 60°, 30°) akquiriert. SNR Messungen wurden in Leber, Fett, Muskulatur, Nieren und Milz sowie in einer Wasserprobe und einer Manganlosung (0,6 mmolar) durchgefuhrt. Hieraus wurden entsprechende Kontrastwerte im Verhaltnis zur Leber berechnet. Ergebnis: Mit abnehmenden Refokussierungswinkeln reduzieren sich die gemessenen SNR Werte insbesondere der Gewebe/Proben mit primar hoher Signalintensitat um 35–50% (180° vs. 30°), die SNR Werte der Leber und der Muskulatur hingegen werden nur geringfugig reduziert. Als Folge kommt es zu einer Abnahme der Kontraste zwischen Leber und den ubrigen parenchymatosen Organen bzw. Flussigkeiten. Die Manganlosung mit kurzen T1 und T2 Zeiten weist hingegen eine deutliche Zunahme der SNR mit reduzierten Refokussierungswinkeln auf (ca. 300%). Schlussfolgerung: Die Reduktion des Refokussierungswinkels in TSE Sequenzen fuhrt zu einer Abnahme der SNR-Werte sowie des Kontrastes der Gewebe des Oberbauches. Die Ursache, insbesondere in Zusammenschau mit dem SNR Anstieg der Manganlosung, ist in erster Linie auf einen verstarkten T1 Effekt zuruckzufuhren. Die Auswirkungen auf die Detektion fokaler Leberlasionen ist unklar, der Einsatz der genannten Verfahren sollte jedoch mit entsprechender Vorsicht erfolgen. Korrespondierender Autor: von Falkenhausen M Radiologische Universitatsklinik Bonn, Sigmund Freud Str. 25, 52105 Bonn E-Mail: marcus.von_falkenhausen@ukb.uni-bonn.de

Volumetrische Veränderungen der Mamma während der Radiotherapie@@@Volumetric Changes of the Breast during Radiotherapy. Is a Replanning Necessary for the Electron Boost?: Ist vor Boostbestrahlung mit Elektronen eine Nachplanung erforderlich?

Hintergrund und Ziel:Eine Radiotherapie der Mamma induziert eine Gewebereaktion mit daraus resultierendem Ödem. Dieses Ödem führt zu einer Volumenzunahme der Mamma. Ziel der Studie war es, diese Volumenzunahme zu quantifizieren und deren Einfluss auf die Planung des Elektronenboosts zu analysieren.Patienten und Methodik:Bei 140 Patientinnen mit Mammakarzinom nach brusterhaltender Therapie erfolgte vor, während und/oder nach der Bestrahlung eine CT-Planung, um die Volumenveränderungen während der Bestrahlung zu evaluieren. Die ermittelten CT-Daten wurden unter Verwendung des HELAX-TMS-Planungssystems zur Bestimmung der Dosisverteilung ausgewertet. Die Bestimmung des Brustvolumens erfolgte mittels Interpolationsalgorithmus. Gemessen am Ausgangsvolumen wurden die Patientinnen in drei Subgruppen unterteilt: Gruppe 1 (n = 47): ≤ 670 cm3, Gruppe 2 (n = 46): 671–999 cm3 und Gruppe 3 (n = 47): ≥ 1 000 cm3 Brustvolumen.Ergebnisse:Initial zeigte sich ein mittleres Brustvolumen von 907 cm3 (100–3 073 cm3). Nach Radiotherapie kam es zu einem Anstieg des Brustvolumens um durchschnittlich 81 cm3 auf 988 cm3 (109–3 185 cm3). Signifikant messbare Volumenzunahmen traten ab einer Zielvolumendosis von 40 Gy auf. Bezogen auf die drei Subgruppen ergaben sich folgende mittlere Volumenzunahmen: Gruppe 1: 53 cm3 (3–120 cm3), Gruppe 2: 85 cm3 (20–200 cm3) und Gruppe 3: 105 cm3 (5–340 cm3). Der Zuwachs war in allen drei Gruppen mit einem p-Wert von p < 0,001 hochsignifikant. Je nach Volumenzunahme der Brust resultierte eine Änderung der Herdtiefe um bis zu 1,0 cm.Schlussfolgerung:Aufgrund der interkurrenten Volumenänderungen unter Bestrahlung erscheint eine zweite CT-Untersuchung zur Nachplanung vor Boostbestrahlung sinnvoll. Die zweite CT-Planung sollte ab 40 Gy erfolgen, um das Ödem ausreichend erfassen zu können.Background and Purpose:Radiotherapy can induce tissue reactions with an edema leading to increased breast volume. The aim of the present study was to quantify this increase and analyze its effect on the electron boost technique.Patients and Methods:140 patients with breast cancer treated with breast-conserving surgery underwent CT planning before, during and/or after radiotherapy in order to evaluate breast volume changes due to radiotherapy. CT data were analyzed using the HELAX planning system and dose distribution was assessed. Determination of the breast volume was achieved using an interpolation algorithm. Three subgroups were analyzed: group 1 (n = 47): ≤ 670 cm3, group 2 (n = 46): 671–999 cm3, and group 3 (n = 47): ≥ 1000 cm3 breast volume.Results:The mean initial breast volume was 907 cm3 (100–3073 cm3). After radiotherapy, mean breast volume increased by 81 cm3 to 988 cm3 (109–3185 cm3). Significant changes in volume were observed after a dose of 40 Gy. According to the subgroups mean volume increase was as follows: group 1: 53 cm3 (3–120 cm3), group 2: 85 cm3 (20–200 cm3), and group 3: 105 cm3 (5–340 cm3). This difference was statistically significant for all subgroups (p < 0.001). Corresponding to the volume increase, depth of the boost target volume changed up to 1.0 cm.Conclusion:As radiotherapy may lead to a significant increase in breast volume, it seems appropriate to perform a second planning CT after about 40 Gy in order to optimize dose distribution for boost irradiation.