Standardization of innovative cardiovascular magnetic resonance sequences - Evaluating the reproducibility of different vendors and field strengths

Die kardiovaskuläre MRT (CMR) ist als nicht-invasives Verfahren zur Diagnostik kardiovaskulärer Erkrankungen bereits in die aktuellen Leitlinien integriert. Durch die Entwicklung innovativer Sequenzen konnte das Spektrum klinischer Indikationen in den letzten Jahren zunehmend erweitert werden. Die dreidimensionale zeitaufgelöste Phasenkontrast-MRT (4D-Fluss-MRT) kann durch die Quantifizierung und Visualisierung kardialer Hämodynamik einen wichtigen Beitrag zum Verständnis kardiovaskulärer Pathophysiologie sowie zur Diagnostik und Therapiesteuerung von Erkrankungen leisten. Fast Strain-encoding (fSENC) ermöglicht als neue Methode die Erfassung myokardialen Strains innerhalb weniger Sekunden. Der Transfer dieser Sequenzen in die klinische Routine erfordert ein Bewusstsein für Störfaktoren. Ziel dieser Arbeit ist die Evaluation potenzieller Störfaktoren wie unterschiedliche MRTHersteller oder Feldstärken als Beitrag zur Standardisierung innovativer CMRSequenzen. 15 gesunde Proband*innen wurden mittels 4D-Fluss-MRT an 3T-Scannern dreier verschiedener Hersteller (GE, Philips, Siemens) untersucht. Als hämodynamische Vergleichsparameter wurden Vorwärtsflussvolumen, maximale Flussgeschwindigkeit und Wandscherkräfte in neun Ebenen bestimmt (1). Des Weiteren wurde die aortale Hämodynamik von zehn gesunden Proband*innen via 4D-Fluss-MRT an drei verschiedenen Feldstärken (1,5T, 3T, 7T) sowie drei unterschiedlichen Sequenzen am 1,5T-MRT untersucht (2). Die Reproduzierbarkeit der fSENC wurde ebenfalls an drei MRT-Geräten unterschiedlicher Hersteller bei 15 gesunden Proband*innen evaluiert. Zur Strain-Analyse wurden globaler zirkumferentieller Strain und globaler longitudinaler Strain genutzt (3). Zusätzlich wurden Scan-Rescan-Reproduzierbarkeit und Intra- und Interobserver-Variabilität beurteilt (1-3). Die hämodynamischen Parameter in der 4D-Fluss-MRT unterschieden sich signifikant zwischen den Scannern dreier verschiedener Hersteller und überschritten jeweils den durch die Intraobserver-Analyse definierten Äquivalenzbereich (1). Die Darstellung der 4D-Fluss-MRT gelang bei allen Feldstärken mit suffizienter Bildqualität. Die Ergebnisse aller hämodynamischen Parameter waren zwischen den Feldstärken ebenfalls nicht äquivalent (2). In den fSENC-Messungen zeigte sich zwischen den drei MRT-Geräten ein geringer, jedoch statistisch signifikanter Bias (3). Die Scan-Rescan- sowie Intra- und Interobserver-Reproduzierbarkeit erzielten gute bis exzellente Ergebnisse (1-3). Zusammenfassend werden durch die spezifischen Protokolle an MRT-Geräten unterschiedlicher Hersteller oder Feldstärken signifikante Unterschiede in den Ergebnissen innovativer CMR-Sequenzen hervorgerufen. Diese Erkenntnis sollte insbesondere bei der Durchführung multizentrischer Studien und Follow-up-Untersuchungen beachtet werden. Für eine optimierte Etablierung in der klinischen Routine ist eine weitere Standardisierung dieser Sequenzen daher essenziell.Cardiovascular magnetic resonance (CMR) has already been established in current guidelines as a non-invasive method for diagnosis of cardiovascular diseases. The development of innovative sequences has fostered an increase in the range of clinical indications during the past years. Three-dimensional time-resolved phase-contrast magnetic resonance (4D Flow MR) enables quantification and visualization of cardiac hemodynamics and may help in understanding cardiovascular pathophysiology as well as in diagnostics and therapy guiding of diseases. Fast strain-encoding (fSENC) is a novel method that allows the acquisition of myocardial strain within a few seconds. Transferring these sequences into clinical routine requires an awareness of confounders. The aim of this work is the evaluation of potential confounders such as different MRI vendors or field strengths as a contribution to the standardization of innovative CMR sequences. 15 healthy volunteers underwent 4D Flow MR examinations at 3T scanners of three different vendors (GE, Philips, Siemens). Forward flow volume, peak velocity and wall shear stress as hemodynamic parameters were investigated in nine planes (1). Furthermore, the aortic hemodynamics of ten healthy volunteers were examined using 4D Flow MR at three different field strengths (1.5T, 3T, 7T) and three different sequences on 1.5T MRI (2). The reproducibility of fSENC was also evaluated on three scanners from different vendors in 15 healthy volunteers. Global circumferential strain and global longitudinal strain were determined for strain analysis (3). In addition, scan-rescan reproducibility as well as intra- and interobserver variability were examined (1-3). 4D flow derived hemodynamic parameters differed significantly between scanners of the three different vendors and exceeded the equivalence range defined by intraobserveranalysis (1). 4D Flow MR displayed sufficient image quality at all field strengths. The results of all hemodynamic parameters were also non-equivalent between field strengths (2). In the fSENC measurements, there was a slight but statistically significant bias between the three scanners (3). Scan-rescan as well as intra- and interobserver reproducibility yielded good to excellent results (1-3). In summary, specific protocols used at scanners from different vendors or field strengths lead to significant differences in the results of innovative CMR sequences. This finding should be taken into account when conducting multi-center studies or patient’s follow-up examinations. Further standardization of these sequences is essential for implementation in clinical routine

SOLUTIONS FOR THE FRACTIONAL MATHEMATICAL MODELS OF DIFFUSION PROCESS

In this research we present two new approaches with Laplace transformation to form the truncated solution of space-time fractional differential equations (STFDE) with mixed boundary conditions. Since order of the fractional derivative of time derivative is taken between zero and one we have a sub-diffusive differential equation. First, we reduce STFDE into either a time or a space fractional differential equation which are easier to deal with. At the second step the Laplace transformation is applied to the reduced problem to obtain truncated solution. At the final step using the inverse transformations, we get the truncated solution of the problem we consider it. Presented examples illustrate the applicability and power of the approaches, used in this study

Paroxysmal Amnesia Attacks due to Hashimoto’s Encephalopathy

Hashimoto’s encephalopathy is a rare disease which is thought to be autoimmune and steroid responsive. The syndrome is characterized by cognitive impairment, encephalopathy, psychiatric symptoms, and seizures associated with increased level of anti-thyroid antibodies. The exact pathophysiology underlying cerebral involvement is still lesser known. Although symptoms suggest a nonlesional encephalopathy in most of the cases, sometimes the clinical appearance can be subtle and may not respond to immunosuppressants or immunomodulatory agents. Here we report a case who presented with drowsiness and amnestic complaints associated with paroxysmal electroencephalography (EEG) abnormalities which could be treated only with an antiepileptic drug

Intersection of different disciplines: Elements

AbstractThis study aims to reveal the extent to which 7th grade students are able to integrate the “use of elements” topic into different disciplines, to determine their way of accomplishing this integration. The study is conducted with 37 seventh grade students in a private school in Istanbul in 2008–2009. Integration of Elements Test (IET) is administered both as a pretest and a posttest and activity sheets are formed to be used during the treatment. After the completion of the treatment, a semi-structured interview is conducted with 4 randomly selected students and they are videotaped and analyzed qualitatively

Spondiloartrit hastalarının fizik aktivitesi ve egzersiz algısı: Kesitsel bir çalışma

Objective: Exercise is a cornerstone in the management of spondyloarthritis (SpA). The aim of this research was to compare the levels of physical activity (PA) and perceived advantages and barriers to exercise of SpA patients with population controls.Methods: In this cross-sectional study 200 patients (118 males, 82 females) and 100 controls (50 males, 50 females) were included. Levels of PA were evaluated using the International Physical Activity Questionnaire-Short Form and perceptions of exercise were assessed using Exercise Benefits and Barriers Scale. Fatigue, psychological status and quality of life of all participants were questioned. Disease activity, functions and mobility of the patients were also assessed. Correlations were analyzed between disease parameters and perceptions of exercise.Results: PA levels were similar on both groups. Of the patients 65% met recommended amount of exercise. Deterioration of psychological status and quality of life were associated with decreased PA levels of the patients. Patients reported fatigue and lack of time barriers more than controls. When disease activity, functionality, mobility, fatigue, psychological status and quality of life of the patients deteriorated, perceived barriers to exercise increased.Conclusion: Health professionals should focus on personal barriers to improve exercise behavior in SpA patients.Amaç: Egzersiz spondiloartritlerin (SpA) yönetiminde bir köşe taşıdır. Bu araştırmanın amacı, SpA hastalarının fiziksel aktivite (PA) düzeylerini ve egzersizden algılanan avantajları ve engelleri popülasyon kontrolleriyle karşılaştırmaktır. Yöntemler: Bu kesitsel çalışmaya 200 hasta (118 erkek, 82 kadın) ve 100 kontrol (50 erkek, 50 kadın) dahil edildi. PA seviyeleri Uluslararası Fiziksel Aktivite Anketi-Kısa Form ile değerlendirildi ve egzersiz algıları Egzersiz Faydaları ve Engeller Ölçeği ile değerlendirildi. Tüm katılımcıların yorgunluğu, psikolojik durumu ve yaşam kalitesi sorgulandı. Hastaların hastalık aktivitesi, fonksiyonları ve mobilitesi de değerlendirildi. Hastalık parametreleri ve egzersiz algıları arasındaki korelasyonlar incelendi. Bulgular: PA seviyeleri her iki grupta da benzerdi. Hastaların %65’i tavsiye edilen egzersiz miktarını karşıladı. Psikolojik durumun ve yaşam kalitesinin bozulması, hastaların PA düzeylerinin azalması ile ilişkiliydi. Hastalar yorgunluk ve zaman yokluğu bariyerini kontrollere göre daha fazla bildirdi. Hastaların hastalık aktivitesi, işlevselliği, hareketliliği, yorgunluğu, psikolojik durumu ve yaşam kalitesi kötüleştiğinde, egzersizin önündeki algılanan engeller arttı. Sonuç: Sağlık çalışanları, SpA hastalarında egzersiz davranışını iyileştirmek için algılanan kişisel engellere odaklanmalıdır

CARBON MONOXIDE EXPOSURES ADMITTED TO EMERGENCY DEPARTMENT:

Amaç: Çalışmamızın amacı, hastanemiz Acil Servisi'ne başvuran Karbonmonoksit (CO) maruz kalımlarının değerlendirilmesiydi. Gereç ve yöntem: Çalışmamızda 1993-2006 yılları arasında Acil Servisimize CO gazı maruziyeti nedeniyle başvuran hastaların dosyaları değerlendirildi. Hastaların yaşları, cinsiyetleri, maruz kalım nedenleri, mevsimlere gore CO gazı kaynakları, klinik bulguları, uygulanan tedavi yöntemleri, hastanede kalış süresi ve zehirlenmelerin sonuçları değerlendirildi. Bulgular: Soba kaynaklı CO maruz kalımları kış aylarında anlamlı oranda yüksekti (p=0,0017, χ2=9,826). Klinik bulgular çocuklarda (%53,6) ve erişkinlerde (%61,4) çoğunlukla hafifti. Orta şiddetli ve ciddi CO maruz kalım olguları, hafif CO maruz kalımlarına göre hastanede daha uzun süre izlendi (p=0,01). İlaç ve Zehir Danışma Merkezimizin Hiperbarik Oksijen Tedavisi (HBO) önerdiği ve HBO tedavisi alan hastalarda, hastanede kalış süresi, HBO tedavisi uygulanamayanlara göre daha kısaydı (p=0,01). Sonuç: Çalışmamızda CO maruz kalımlarında HBO alanlarda, Normobarik oksijen tedavisi (NBO) alanlara gore hastanede yatış süresi kısa bulunmasına karşın hasta sayısının az olması nedeniyle, HBO tedavisinin üstünlüğünü söylemek olanaklı değildir. CO zehirlenmesinde HBO tedavisinin NBO'e göre daha etkili olduğunun araştırılması için daha fazla hastanın dahil edildiği çok merkezli çalışmalara gereksinim vardır. Objective: The aim of the study was to analyze carbon monoxide (CO) exposures that were admitted to our hospital's Emergency Sevice (ES). Matherial and method: CO exposure cases admitted to ES between 1993 and 2006 were evaluated. The files of patients were scanned. Age, sex, exposure reason, sources according to seasons, clinical signs, methods of management, length of hospital stay and outcome were evaluated. Results: Poisoning caused by woodstove based CO exposures was common in winter (p=0.0017, χ2=9.826). Clinical manifestations were mostly mild (53.6%) both in children (61.4%) and in adults. Moderate and severe CO poisoning cases were observed longer in hospital than that of mild CO exposures (p=0.01). In cases who were recommended and given Hyperbaric oxygen treatment (HBO) therapy, follow-up duration in the hospital was shorter than that of patients who recommended and could not be given HBO therapy (p=0.01). Conclusion: It is difficult to suggest that HBO therapy might shorten the hospitalization period in CO exposure, because of small number of patients. To evaluate the HBO treatment and hospitalization duration relation, prospective multicenter studies with larger number of CO exposed patients are needed

Farede prematüre over yetmezliğinde mTERT telomeraz katalitik alt ünitesinin rolünün belirlenmesi

Memelilerde prenatal hayatta oluşan oosit rezervi, postnatal hayatta azalarak tükenmektedir. Foliküler atrezi olarak adlandırılan bu mekanizma ile ovariyal yaşlanma meydana gelmektedir. Primordiyal folikül havuzu tekrardan yenilenemediği için bu tükeniş sonucunda infertilite ya da Prematüre Over Yetmezliği (POY) ile karşı karşıya kalınmaktadır. Polisiklik aromatik hidrokarbon 7, 12-dimetilbenz (7,12-dimethylbenz-[a]anthracene (DMBA)), ovaryum da dahil olmak üzere pekçok tümörü tetikleyen ve günlük hayatta da sıklıkla maaruz kaldığımız bir çevresel karsinojendir. Telomeraz, hücrenin bölünmesi esnasında kromozomların kararlı yapılarının korunmasını sağlar ve fare telomeraz ters transkriptaz (mTERT), telomeraz kompleksinin gerekli bir bileşenidir. c-Abl protein tirozin kinaz, DNA çift sarmalında kırıkların oluşması ile aktive olan ve telomer kontrolü esnasında bu kırıkların tamir edilmesine katılan bir proteindir. Telomer kısalması, hücre bölünmesini zamanla durduran bir işlemdir. Bu nedenle çalışmamızda DMBA indüklü ovotoksisite sonucu oluşan POY’de c-Abl ve mTERT’in önemli bir role sahip olabileceğini düşünmekteyiz. Buradan yola çıkarak günlük yaşamda sürekli olarak maaruz kalınan DMBA’nın ovaryumdaki oosit rezervi, oosit kalitesi ve granuloza hücreleri üzerindeki etkisini c-Abl (Abelson Tirozin Kinaz) ve mTERT (telomeraz katalitik altünitesi) belirteçleri ile açıklamayı hedefledik. Çalışmamızda postnatal (PND) 28 günlük BalbC türü farelere 7 gün boyunca susam yağı içerisinde çözülen 1mg/kg DMBA uygulaması yapıldı. İzole edilen ovaryum dokularında Hematoksilen-Eozin boyama ile morfolojik değerlendirme ve folikül sayımı yapıldı. İmmünofloresan yöntemi ile c-Abl ve mTERT lokalizasyonları gösterildi. Ayrıca ELISA, western blot ve qRT-PCR yöntemleri kullanılarak fare ovaryumunda DMBA tedavisinin telomeraz aktivitesi üzerine olan etkisi gösterildi. Ayrıca, Transmisyon Elektron Mikroskobi yöntemi ile oosit-granuloza hücresi arasındaki ilişki ultrastrüktürel düzeyde incelendi. Çalışmamızda DMBA indüklü ovotoksisite sonucu oluşan POY’de c-Abl ve mTERT, ilk defa gösterilmiştir. Bu proje ile DMBA uygulanmış fare ovaryumunda c-Abl ve mTERT ekspresyonlarındaki değişimin gösterilmesiyle, projemizin sonuçlarının POY’de erken over yaşlanması ve kadın infertilitesine ilişkin sinyal mekanizmalarına ışık tutacağını düşünmekteyiz.(TÜBİTAK-215S867)

Traveling Volunteers: A Multi‐Vendor, Multi‐Center Study on Reproducibility and Comparability of 4D Flow Derived Aortic Hemodynamics in Cardiovascular Magnetic Resonance

Background: Implementation of four-dimensional flow magnetic resonance (4D Flow MR) in clinical routine requires awareness of confounders. Purpose: To investigate inter-vendor comparability of 4D Flow MR derived aortic hemodynamic parameters, assess scan-rescan repeatability, and intra- and interobserver reproducibility. Study type: Prospective multicenter study. Population: Fifteen healthy volunteers (age 24.5 ± 5.3 years, 8 females). Field strength/sequence: 3 T, vendor-provided and clinically used 4D Flow MR sequences of each site. Assessment: Forward flow volume, peak velocity, average, and maximum wall shear stress (WSS) were assessed via nine planes (P1-P9) throughout the thoracic aorta by a single observer (AD, 2 years of experience). Inter-vendor comparability as well as scan-rescan, intra- and interobserver reproducibility were examined. Statistical tests: Equivalence was tested setting the 95% confidence interval of intraobserver and scan-rescan difference as the limit of clinical acceptable disagreement. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used for scan-rescan reproducibility and intra- and interobserver agreement. A P-value 0.9: excellent, 0.75-0.9: good). Results: Ten volunteers finished the complete study successfully. 4D flow derived hemodynamic parameters between scanners of three different vendors are not equivalent exceeding the equivalence range. P3-P9 differed significantly between all three scanners for forward flow (59.1 ± 13.1 mL vs. 68.1 ± 12.0 mL vs. 55.4 ± 13.1 mL), maximum WSS (1842.0 ± 190.5 mPa vs. 1969.5 ± 398.7 mPa vs. 1500.6 ± 247.2 mPa), average WSS (1400.0 ± 149.3 mPa vs. 1322.6 ± 211.8 mPa vs. 1142.0 ± 198.5 mPa), and peak velocity between scanners I vs. III (114.7 ± 12.6 cm/s vs. 101.3 ± 15.6 cm/s). Overall, the plane location at the sinotubular junction (P1) presented most inter-vendor stability (forward: 78.5 ± 15.1 mL vs. 80.3 ± 15.4 mL vs. 79.5 ± 19.9 mL [P = 0.368]; peak: 126.4 ± 16.7 cm/s vs. 119.7 ± 13.6 cm/s vs. 111.2 ± 22.6 cm/s [P = 0.097]). Scan-rescan reproducibility and intra- and interobserver variability were good to excellent (ICC ≥ 0.8) with best agreement for forward flow (ICC ≥ 0.98). Data conclusion: The clinical protocol used at three different sites led to differences in hemodynamic parameters assessed by 4D flow. Level of evidence: 2 TECHNICAL EFFICACY STAGE: 2

Our Cases of Secondary Narcolepsy with Three Different Etiology: Review of the Literature

Narcolepsy is neurological disorder classified among central hypersomnolences group and characterized by excessive daytime sleepiness, cataplexy, associated symptoms like hypnogogic/hypnopompic hallucinations and sleep paralysis. It is divided into two types on the basis of accompanying cataplexy. In the pathophysiology of this disorder, which is accused an autoimmune process, hypocretin deficiency in the hypothalamus was shown. Narcolepsy is often seen as a primary disease in young population but may also occur with other disorders like cerebrovascular diseases, intracranial tumors, encephalitis, sarcoidosis, multiple sclerosis or after head trauma, infections, and vaccines; in which the disease is accepted as secondary narcolepsy. In this case report, patients presenting with excessive daytime sleepiness and diagnosed as having secondary narcolepsy due to medical causes, and who have Parkinson’s disease (PD), history of interferon use and hypothalamic involvement associated with Langerhans cell histiocytosis (LCH) were reported. Daytime sleepiness complaints should be well questioned in organic pathologies related with hypothalamus-pituitary system such as PD and similar diseases or in patients with history of drug use and secondary narcolepsy should be beared in mind

Comparison of dermoscopic and histopathologic diagnoses of naevus naevocellularis

Melanositik pigmente deri lezyonlarının birbirinden ayırımı, planlanacak tedavi yaklaşımı açısından önemlidir. Bu amaçla yapılacak histopatolojik incelemeye alternatif olarak son zamanlarda preoperatif tanısal doğruluğu belirgin arttıran dermoskopi yöntemi olarak ön plana çıkmıştır. Bu çalışmada, sıkça karşılaştığımız melanositik pigmente lezyonlardan olan nevus nevosellularislerde dermoskopinin histopatolojik incelemenin yerine geçip, geçemeyeceği araştırılmıştır. Çalışmamızda, Eylül 1998- Haziran 1999 tarihleri arasında Celal Bayar Üniversitesi Tıp Fakültesi Dermatoloji Anabilim Dalı Ben Takip Polikliniği' ne başvuran 22 hastadaki toplam 25 nevus nevosellularis dermoskopik olarak incelendikten sonra alınan biyopsi materyallerinin histopatolojik tetkiki yapılmış ve her iki yöntemle konulan tanılar karşılaştırılmıştır. Dermoskopik muayenede el dermatoskopu, slayt çekimlerinde Dermaphot kullanılmıştır. Dermatoskopi ve histopatoloji yöntemlerinin tutarlılığını ölçmek için Kappa analizi yapılmıştır. Dermoskopik olarak 7 jonksiyonel nevus naevocellularis (NNC), 15 bileşik NNC, 3 intradermalNNC tanısı konulurken, histopatolojik olarak 7 jonksiyonel NNC, 10 bileşik NNC, 8 intradermal NNC tanısı konulmuştur. Dermoskopik olarak 25 lezyonun 20'si (%80), histopatolojik tanıyla aynı tanıyı almıştır. Kappa istatistiğinde iki yöntemle konulan tanıların iyi derecede tutarlı olduğu bulunmuştur (K= 0.69). Noninvaziv tanı yöntemi olarak son yıllarda ön plana çıkan dermoskopinin melanositik pigmente deri lezyonlarından nevus nevosellularislerin tanısında ve ayrımında histopatolojik incelemenin yerine geçemeyeceği sonucuna varılmıştır.Differential diagnosis in melanocytic skin lesions is important in determining the treatment modality. In the past, histopathologic examination was mostly used for this aim. Recently, dermoscopy is widely used as an alternative noninvasive diagnostic method, so that it increases preoperative diagnostic accuracy. In this study our aim was to determine whether dermoscopy can substitute for histopathologic examination in the diagnosis of naevus naevocellularis. 25 naevus naevocellularis of 22 patients, who had admitted to our nevus follow-up clinic between September 1998-June 1999, were enrolled in this study. After dermoscopic and histopathologic examinations of all the lesions were completed, the concordance between dermoscopic and histopathologic diagnoses were evaluated. Manual dermoscope was used for routine dermoscopic examinations. Finally, dermoscopic photographs of the lesions were taken by Dermaphot. Kappa value was interpreted to assesss the agreement between dermoscopic and histopathologic methods. Dermoscopic examination revealed 7 jonksiyonel nevus naevocellularis (NNC), 15 bileþik NNC, 3 intradermal NNC, where as histopathologic examination revealed 7 jonksiyonel NNC, 10 bileþik NNC, 8 intradermal NNC. Of the 25 lesions dermoscopically examined, the diagnoses of 20 (80%) were concordant with the histopathologic diagnoses. The agreement between dermoscopic and histopathologic methods was good (K value= 0.69). Although dermoscopy is widely used as an alternative noninvasive diagnostic method in the differential diagnosis of melanocytic skin lesions recently, our results have led us to conclude that this popular method can not substitute for histopathologic examination in the diagnosis of naevus naevocellulari