Značaj difuzionog imidžinga u protokolu magnetnorezonantne enterografije u dijagnostici Kronovog enteritisa
The significance of diffusion imaging in the protocol of magnetic resonance enterography in the diagnosis of Crohn᾿s disease
Докторанд
Пилиповић-Грубор, ЈеленаМентор
Stojanović, SanjaOstojić, Jelena
Чланови комисије
Nikolić, OliveraPetrović, Slađana
Nićiforović, Dijana
Veljković, Radovan
Savić, Željka
Метаподаци
Приказ свих података о дисертацијиСажетак
UVOD: Kronov enteritis je dugogodišnja, hronična destruktivna zapaljenska bolest gastrointestinalnog trakta sa nepredvidivim epizodama akutizacije bolesti i periodima remisije. Tačna procena aktivnosti bolesti se zasniva na kombinaciji kliničkog i endoskopskog skora, laboratorijskih nalaza i nalaza dijagnostičkih procedura, prevashodno pregleda creva magnetnom rezonancom (magnetnorezonanantna enterografija, MRE) koja u svom protokolu sadrži DWI sekvencu. S obzirom da se KE uglavnom javlja kod mlađih pacijenata i zahteva ponavljanje dijagnostičkih procedura tokom života, MRE danas predstavlja dijagnostičku metodu izbora. Kvantitativnom analizom dobijenih MR imidža, ADC (Apparent diffusion coefficient) mape i izračunavanjem DWI MaRIA (DWI magnetic resonance index activity) skora objektivno se procenjuje stepen aktivnosti zapaljenja zida (inaktivna faza, blaga/umereno teška, teška aktivna faza) što je neophodno za planiranje adekvatne terapije koja ima za cilj dug period remisije, prevenc...iju nastanka komplikacija i sprečavanje progresije bolesti. Kod ponavljanih pregleda magnetnom rezonancom uz primenu intravenskog paramagnetnog kontrastnog sredstva dolazi do nagomilavanja gadolinijuma u moždanom parenhimu, a klinički efekat ove pojave je i dalje nepoznat što zahteva oprez prilikom odluke o primeni intravenskog kontrastnog sredstva. CILJ: Ispitivanje dijagnostičke vrednosti difuzije, kao dopunske funkcionalne metode za karakterizaciju tkiva, u protokolu MRE kod Kronovog enteritisa, kao i ispitivanje mogućnosti kvantitativne difuzije (ADC koeficijenta, DWI MaRIA skora) u razlikovanju aktivne od hronične faze bolesti u odnosu na mogućnosti konvencionalnih T1 sekvenci što bi moglo značajno da doprinese povećanju efikasnosti MR pregleda, bezbednosti i uštedi potrošnog materijala. MATERIJAL I METODE: Ova retrospektivno-prospektivna studija je obuhvatila 50 ispitanika sa patohistološki dokazanim Kronovim enteritisom koji prethodno nisu imali resekciju creva i koji su bili ili u fazi simptomatske bolesti ili u fazi monitoringa KE tokom terapijskog tretmana, upućeni na MR pregled od strane gastroenterologa. Svim ispitanicima je načinjen MRE pregled na aparatu za magnetnu rezonancu jačine magnetnog polja 1.5T (Signa HDxT, General Electric Healthcare, Boston, SAD) u Centru za radiologiju Kliničkog centra Vojvodine. MRE pregled je rađen prema protokolu koji čine aksijalne i koronalne T2W sekvence sa i bez gašenja masti, aksijalna i koronalna DWI sekvenca sa visokim b-vrednostima, nativna T1W sekvenca, dinamska koronalna T1W sekvenca nakon primene intravenskog kontrastnog sredstava, potom aksijalna i koronalna T1W sekvenca. Pre nativne T1W sekvence ispitanici su intravenski primili spazmolitik (1ml Buscopan-a od 20 mg) u cilju usporavanja crevne peristaltike, a nakon nativne T1W sekvence intravensko paramagnetno kontrastno sredstvo. Potom je načinjena koronalna dinamska T1W sekvenca, zatim koronalna i aksijalna T1W sekvenca. U postprocesingu je kod svih ispitanika izvršena segmentna MRE analiza tako što je tanko i debelo crevo podeljeno u sedam segmenata: jejunum, proksimalni ileum, distalni ileum, cekum i ascedentni kolon, transverzalni kolon, descedentni kolon i sigmoidni kolon i rektum, odnosno ukupno je ispitano 350 segmenata creva. Na svakom segmentu je izvršena kvantitativna analiza DWI imidža (merenje vrednosti koeficijenta difuzije na ADC mapi) bilo da su postojali znaci restrikcije difuzije ili ne. Upoređivale su se vrednosti ADC mape između istih segmenata creva (npr. proksimalni ileum sa proksimalnim ileumom...). Potom je kod svih segmenata izvršena analiza T2W imidža, dok je kod patoloških segmenata izvršena analiza nativnih T1W imidža i T1W imidža nakon primene intravenskog kontrastnog sredstva, kao i kvantitativna analiza stepena porasta intenziteta signala izračunavanjem prema referentnoj formuli iz literature. Na patološki izmenjenim segmentima su se izračunavali kvantitativni indeksi aktivnosti Kronovog enteritisa na MRE: MaRIA (Magnetic resonance index of activity) i DWI MaRIA skorovi, takođe prema referentnim formulama. Kontrolnu grupu su činila 42 segmenta creva koja po svojim morfološkim karakteristikama (na nativnim T2W imidžima, DWI imidžima i T1W imidžima nakon primene intravenskog kontrastnog sredstva) nisu imala patološki izgled, odnosno imala su izgled zdravih segmenata koji nisu bili u neposrednom kontaktu sa patološki izmenjenim segmentom. U statističkoj obradi podataka koristile su se statističke metode i postupci koji se koriste u metodološki sličnim medicinskim istraživanjima, kao što su univarijantni postupci (t-test, Roy-ev test, Pirsonov test koeficijent kontigencije, koeficijent multiple korelacije (R)) i multivarijantni postupci MANOVA i diskriminativna analiza. Na neparametrijskim veličinama izvršeno je skaliranje podataka na tabelama kontigencije. REZULTATI: Najviše vrednosti ADC koeficijenta zdravog segmenta su izmerene na proksimalnom delu ileuma, dok su najniže vrednosti izmerene na sigmoidnom delu kolona i rektumu. Daljom analizom između lokacija zdravih segmenata dobili smo da je u odnosu na vrednost ADC koeficijenta najmanje rastojanje bilo između transverzalnog i ascedentnog dela kolona, a da su najudaljenije lokacije sigmoidni deo kolona i rektum i proksimalni deo ileuma. Kod pacijenata sa Kronovim enteritisom postoji značajna razlika i jasno definisana granica između vrednosti ADC koeficijenta zdravih u odnosu na patološke segmente creva, bez obzira da li je patološki izmenjen segment aktivno ili hronično inflamatorno izmenjen. Analizom patoloških segmenata creva dobijene su najniže vrednosti ADC koeficijenta izmerene na distalnom i terminalnom ileumu. Poređenjem MaRIA i DWI MaRIA grupa za inaktivnu fazu bolesti dobijeno je neslaganje između vrednosti MaRIA i DWI MaRIA skorova u odnosu na merene parametre: vrednosti DWI MaRIA skora, pa i izmerene vrednosti ADC koeficijenta su bile očekivane i u skladu sa podacima iz literature, dok su vrednosti MaRIA skora bile više od očekivanih. Vrednost DWI MaRIA skora < 8,4 je bila pouzdanija za dokazivanje odsustva aktivne faze KE od vrednosti MaRIA skora < 7. Poređenjem MaRIA i DWI MaRIA grupa za težak oblik aktivne faze KE vrednosti ADC koeficijenta, MaRIA i DWI MaRIA skorova su bile, prema literaturi, očekivane. Poređenjem MaRIA i DWI MaRIA grupa za blaži i težak oblik aktivne faze bolesti nije postojala značajna razlika između vrednosti ADC koeficijenta, ali su razlike bile izražene i značajne između vrednosti DWI MaRIA skora. Klaster grupisanjem MaRIA grupa, srednje vrednosti MaRIA u klaster grupama bile su više nego u MaRIA grupama načinjenim prema smernicama iz literature, uz ravnomerniju raspodelu segmenata creva naročito evidentnu poređenjem grupa za inaktivnu fazu KE. Vrednosti ADC koeficijenta su u svim MaRIA i DWI MaRIA grupama bile slične i nije mogla razlikovati blaga od teškog oblika aktivne faze bolesti. Vrednosti DWI MaRIA skora između MaRIA i DWI MaRIA grupa su bile značajno različite, naročito između MaRIA i DWI MaRIA klaster grupa: vrednost DWI MaRIA je bila bolja (od svih MR parametara) za ralikovanje blagog od teškog stepena Kronovog enteritisa, a klaster grupisanje je doprinelo boljoj diferencijaciji. ZAKLJUČAK: Korišćenje DWI sekvence u protokolu MRE pregleda i izračunavanje vrednosti DWI MaRIA skora značajno unapređuje MRI dijagnostiku Kronovog enteritisa tj. magnetnorezonantna enterografija sa difuzionim imidžingom bez primene intravenskog paramagnetnog kontrastnog sredstva je dovoljno dobra za razlikovanje stepena aktivnosti bolesti i da primena intravenskog kontrastnog sredstva u toku MRE pregleda ne treba da bude rutinska, već samo u slučajevima kliničke i radiološke sumnje na postojanje komplikacija kod težeg oblika zapaljenja zida.
INTRODUCTION: Crohn᾿s enteritis is a long-lasting chronic destructive inflammatory disease of the gastrointestinal tract with unpredictable episodes of disease acutization and periods of remission. An accurate assesment of disease activity is based on combination of clinical and endoscopic scores, laboratory findings and diagnostic procedures, primarily a magnetic resonance examination of the intestine (MR enterography, MRE), with DWI sequence incorporated in the protocol. Considering that Crohn᾿s enteritis mostly occurs in younger patients and requires repeated diagnostic procedures throughout life, the diagnostic method of choice is MR. The quantitative analysis of the obtained MR images, the ADC (Apparent diffusion coefficient) map and calculation of the DWI MaRIA (DWI magnetic resonance index activity) score objectively assesses the degree of wall inflammation activity (inactive phase, mild/moderately severe, severe active phase), which is necessary for adequate therapy planning ai...med at a long-term period of remission, prevention of complications and disease progression. Repeated magnetic resonance examinations with the administration of intravenous paramagnetic contrast medium, leads to accumulation of gadolinium in the brain parenchyma. The clinical effect of this phenomena is still unknown, which requires caution when deciding on the use of intravenous contrast medium. OBJECTIVE: Examine the diagnostic value of diffusion, as a supplementary functional method for tissue characterisation, in the MRE protocol in Crohn᾿s enteritis, as well as to examine the possibility of quantitative diffusion (ADC coefficient, DWI MaRIA score) in differentiating the active from the chronic phase of disease, compared to conventional T1 sequences, which could significantly contribute to increased efficiency of MR examinations, safety and reduced expenses. MATERIAL AND METHODS: This retrospective-prospective study included 50 subjects with pathohistologically proven Crohn᾿s enteritis who hadn᾿t previously undergone bowel resection and who were either in symptomatic phase or in monitoring phase and reffered for a MR enterography by a gastroenterologyst. All subjects underwent MRI examination on a magnetic resonance mashine with a magnetic field strenght of 1.5T (Signa HDxT, General Electric Healthcare, Boston,USA) at Center of Radiology, Clinical Center of Vojvodina. The MRE examination was performed accoring to a protocol comprising axial and coronal T2W sequences with and without fat suppression, axial and coronal DWI sequences with high b-values, non-contrast coronal T1W sequence, dynamic coronal T1W sequence after administration of intravenouse contrast agent, followed by axial and coronal T1W sequence. Before the non-contrast T1W sequence acquisions, the subject received an intravenous antispasmodic (1ml Busopan of 20mg) in order to slow down intestinal peristalsis, and after non contrast T1W sequence intravenous paramagnetic contrast medium. Than, coronal dynamic T1W sequence was performed, followed by coronal and axial T1W sequences. In post-processing a segmental MRI analysis was perfomed on all subjects by dividing the small and large intestine into seven segments: jejunum, proximal ileum, distal ileum, cecum and ascending colon, transverse colon, descending colon and sygmoid colon and rectum, i.e. 350 intestinal segments were examined. A quantitative analysis of DWI image was performed on each segment (measurement of the value of the diffusion coefficient on the ADC map) assessing whether there were signs of diffusion restriction or not. ADC map values were compared between the same intestinal segments (eg proximal ileum with proximal ileum...). Than, in all segments T2W images were analyzed, while in pathological segments non-contrast T1W images and T1W images after administration of intravenouse contrast medium were analyzed, together with a quantitative analysis of the degree of signal intensity increase by calculation accoring to the reference formula from the literature. Quantitative indices of Crohn᾿ enteritis were calculated on the pathologically altered segments on MRE: MaRIA (Magnetic resonance index of activity) and DWI MaRIA scores, also accoring to the reference formulas. The control group were 42 intestinal segments that didn᾿t have pathologycal appearence accoring to their morphological characteristics (on non-contrast T2W images, DWI image and post-contrast T1W images), i.e. they had the appearence of healthy segments that were not in direct contact with pathologically altered segment. Statistical methods and procedures used in methodologically similar medical research, such as univariate procedures, were used in statistical data precessing (t-test, Roy᾿s test, Pearson᾿s test contigency coefficient, multiple correlation coeficient (R)) and multivariate MANOVA procedures and discriminant analysis. Data scaling on contigency tables was performed on non-parametric quantities. RESULTS: The highest values of the ADC coefficient of the healthy segment were measured in the proximal part of the ileum, while the lowest values were measured in the sigmoid part of the colon and rectum. Further analysis of healthy segments locations showed that,in relation to the ADC coefficient value the smallest distance was between transverse and ascending part of the colon, and that the most distant locations were between the sigmoid part of the colon and rectum and the proximal part of the ileum. There is a statistically significant difference and clearly defined boundary between the values of the ADC coefficient of healthy versus pathological segments of the intestine, regardless of whether they are patological segments with signs of chronic an/or active wall inflammation in patients with CB. Analysisof pathological segments of the intestine revealed the lowest values of the ADC coefficient measured in the distal and terminal ileum. By comparing MaRIA and DWI MaRIA groups for the inactive phase of the CB there was a discrepancy between the values of the MaRIA and DWI MaRIA score in relation to the measured parameters: the values of DWI MaRIA score and the measured values of the ADC coefficient were expected and in accordance with the data from the literature, while the values of the MaRIA score were higher than expected. A DWI MaRIA values < 8.4 was mor reliable for proving the absence of active phase CB than a MaRIA score value < 7. By comparing MaRIA and DWI MaRIA groups for the severe form of active phase of the CB, the expected values of the ADC coefficient, MaRIA and DWI MaRIA scores were obtained, accoring to the literature. Comparison of MaRIA and DWI MaRIA groups for the mild and severe form of active phase of the disease, showed no significant difference between the values of the ADC coefficient, but the differences were pronounced and significant between the values of DWI MaRIA score. By clustering the MaRIA groups, the mean MaRIA values in a cluster groups were higher than in MaRIA groups that were made accoring to the instructions from the literature, with a more even distribution of the bowel segments especially visible when comparing the groups for the inactive phase of CB. The values of the ADC coefficient in all MaRIA and DWI MaRIA groups were similar and could not distinguish mild from severe forms of the active phase. Values of the DWI MaRIA score between MaRIA and DWI MaRIA groups were significantly different, especially between MaRIA and DWI MaRIA cluster groups – it was better (of all MR variables) for differentiating mild from severe form of CB, and clustering contributed to better differentiation. CONCLUSION: Using the DWI sequence in the MRE protocol and calculating DWI MaRIA score significantly improves the MRI diagnosis of Crohn᾿s enteritis – MRE with diffusion imaging without the use of intravenouse paramagnetic contrast medium is sufficient for estimating the degree of disease activity. Therefore, the use of intravenouse contrast medium during MRE examination should not be applied routinely, but only in cases of clinical and radiological suspicion of the existence of complications in severe form of active disease.