A better understanding of tumour heterogeneity is central for accurate diagnosis, targeted therapy and personalised treatment of glioblastoma patients. This thesis aims to investigate whether pre-operative multi-parametric magnetic resonance imaging (MRI) can provide a useful tool for evaluating inter-tumoural and intra-tumoural heterogeneity of glioblastoma. For this purpose, we explored: 1) the utilities of habitat imaging in combining multi-parametric MRI for identifying invasive sub-regions (I & II); 2) the significance of integrating multi-parametric MRI, and extracting modality inter-dependence for patient stratification (III & IV); 3) the value of advanced physiological MRI and radiomics approach in predicting epigenetic phenotypes (V). The following observations were made: I. Using a joint histogram analysis method, habitats with different diffusivity patterns were identified. A non-enhancing sub-region with decreased isotropic diffusion and increased anisotropic diffusion was associated with progression-free survival (PFS, hazard ratio [HR] = 1.08, P < 0.001) and overall survival (OS, HR = 1.36, P < 0.001) in multivariate models. II. Using a thresholding method, two low perfusion compartments were identified, which displayed hypoxic and pro-inflammatory microenvironment. Higher lactate in the low perfusion compartment with restricted diffusion was associated with a worse survival (PFS: HR = 2.995, P = 0.047; OS: HR = 4.974, P = 0.005). III. Using an unsupervised multi-view feature selection and late integration method, two patient subgroups were identified, which demonstrated distinct OS (P = 0.007) and PFS (P < 0.001). Features selected by this approach showed significantly incremental prognostic value for 12-month OS (P = 0.049) and PFS (P = 0.022) than clinical factors. IV. Using a method of unsupervised clustering via copula transform and discrete feature extraction, three patient subgroups were identified. The subtype demonstrating high inter-dependency of diffusion and perfusion displayed higher lactate than the other two subtypes (P = 0.016 and P = 0.044, respectively). Both subtypes of low and high inter-dependency showed worse PFS compared to the intermediate subtype (P = 0.046 and P = 0.009, respectively). V. Using a radiomics approach, advanced physiological images showed better performance than structural images for predicting O6-methylguanine-DNA methyltransferase (MGMT) methylation status. For predicting 12-month PFS, the model of radiomic features and clinical factors outperformed the model of MGMT methylation and clinical factors (P = 0.010). In summary, pre-operative multi-parametric MRI shows potential for the non-invasive evaluation of glioblastoma heterogeneity, which could provide crucial information for patient care.

Diffusion-weighted (DW) magnetic resonance imaging is an important neuroimaging technique that has successful applications in diagnosis of ischemic stroke and methods based on diffusion tensor imaging (DTI). Tensor measures have been used for detecting changes in tissue microstructure and for non-invasively tracing white matter connections in vivo. The most common image acquistion strategy is to use a DW single-shot echo-planar imaging (ss-EPI) pulse sequence, which is attractive due to its robustness to motion artefacts and high imaging speed. However, this sequence has limited achievable spatial resolution and suffers from geometric distortion and blurring artefacts. Readout-segmented echo-planar imaging (rs-EPI) is a DW sequence that is capable of acquiring high-resolution images by segmenting the acquisition of k- space into multiple shots. The fast, short readouts reduce distortion and blurring and the problem of artefacts due to motion-induced phase changes between shots can be overcome with navigator techniques. The rs-EPI sequence has two main shortcomings. (i) The method is slow to produce image volumes, which is limiting for clinical scans due to patient welfare and prevents us from acquiring very many directions in DTI. (ii) The sequence (like other diffusion techniques) is far from the optimum repetition time (TR) for acquiring data with the highest possible signal-to-noise ratio (SNR) in a given time. The work in this thesis seeks to address both of these important issues using a range of approaches. In Chapter 4 a partial Fourier extension is presented, which addresses point (i) by reducing the number of readout segments acquired and estimating the missing data. This allows reductions in scan time by approximately 40&percnt; and the reliability of the images is demonstrated in comparisons with the original images. The application of a simultaneous multi-slice scheme to rs-EPI, to address points (i) and (ii), is described in Chapter 5. Using the slice-accelerated rs-EPI sequence, tractography data were compared to ss-EPI data and high-resolution trace-weighted data were acquired in clinically relevant scan times. Finally, a 3D multi-slab extension that addresses point (i) is presented in Chapter 6. A 3D sequence could also allow higher resolution in the slice direction than 2D multi-slice methods, which are limited by the difficulties in exciting thin, accurate slices. A 3D version of rs-EPI was simulated and implemented and a k-space acquisition synchronised to the cardiac cycle showed substantial improvements in image artefacts compared to a conventional k-space acquisition.

<p>UVOD: Maligni tumori reproduktivnih organa nalaze se među vodećim uzrocima obolevanja i umiranja od malignih bolesti žena, kako u svetu, tako i u Srbiji. Jedan od najvažnijih puteva &scaron;irenja ovih bolesti je limfogeni, a konvencionalna radiolo&scaron;ka dijagnostika limfnih čvorova kod ovih pacijentkinja je neprecizna. Funkcionalna radiolo&scaron;ka dijagnostika, uključujući i magnentno rezonantnu sekvencu difuzionog kretanja (DWI) i iz nje izvedenu ADC mapu koja omogućava kvantitativnu analizu difuzionih osobina unutar limfnog čvora, daju obećavajuće rezultate u mogućnosti razlikovanja benignih od maligno izmenjenih limfnih čvorova male karlice i ingvinuma kod pacijentkinja obolelih od malignih tumora ženskih polnih organa. CILJ: Cilj studije je 1. utvrđivanje dijagnostičkih mogućnosti magnetnorezonantne sekvence difuzionog kretanja (DWI) u razlikovanju benignih od maligno izmenjenih limfnih čvorova male karlice i ingvinuma kod pacijentkinja obolelih od malignih tumora ženskih polnih organa, poređenjem preoperativno načinjenog magnetnorezonantnog pregleda i postoperativnog patohistolo&scaron;kog nalaza; 2. analiza povezanosti osobina metastatski izmenjenih limfnih čvorova na sekvenci difuzionog kretanja (DWI) i gradusa primarnog tumora, i 3. utvrđivanje uticaja tehničkih karakteristika sekvenci difuzinonog kretanja (DWI) na magnetnorezonantu procenu metastatske infiltracije karličnih i ingvinalnih limfnih čvorova i postoperativnog patohistolo&scaron;kog nalaza. MATERIJAL I METODE: Istraživanje je sprovedeno u periodu od 2013. do 2016.godine, kao prospektivna klinička studija u Centru za radiologiju, na Operativnom odeljenju Zavoda za ginekologiju, Klinike za ginekologiju i aku&scaron;erstvo i u Zavodu za patologiju Kliničkog Centra Vojvodine u Novom Sadu. Studija je obuhvatila 80 pacijentkinja obolelih od malignih tumora vulve, vagine, grlića materice, tela materice i jajnika. Na osnovu lokalizacije malignog tumora sve ispitanice su razvrstane u 5 grupa: grupa A- 3 žene obolele od carcinoma vulve, grupa B- 1 žena obolela od karcinoma vagine, grupa C-32 pacijentkinje obolele od karcinoma grlića materice, grupa D- 30 pacijentkinja obolelih od malignih tumora tela materice i grupa E- 14 žena obolelih od malignih tumora jajnika. Procena stadijuma bolesti definitivno je izvr&scaron;ena posle operacije na osnovu histopatolo&scaron;kog pregleda kompletnog hirur&scaron;kog materijala uključujući i pregled uklonjenih limfnih čvorova na osnovu aktuelne FIGO klasifikacije stadijuma bolesti zasebno za svaku pojedinačnu lokalizaciju malignog tumora. Svim pacijentkinjama je preoperativno načinjen magnetnorezonantni pregled male karlice na uređaju za magnetnu rezonancu 1.5 T General Electric Signa HDx u Centru za radiologiju, Kliničkog centra Vojvodine. Kod istih pacijentkinja naknadno je sprovedeno standardno hirur&scaron;ko lečenje po protokolu hirur&scaron;kog lečenja za dato maligno ginekolo&scaron;ko oboljenje sa karličnom i/ili ingvinalnom limfadenektomijom. Postoperativno je izvr&scaron;ena patohistolo&scaron;ka analiza hirur&scaron;ki uklonjenog materijala i limfnih čvorova razdvojenih po anatomskim grupama u karlici i ingvinalnoj regiji. REZULTATI: Ukupno 2320 limfnih čvorova je mapirano i patohistolo&scaron;ki pregledano kod 80 pacijenata. Metastaze u limfnim čvorovima patohistolo&scaron;ki su verifikovane kod 28 pacijenata (35%). Kod ovih 28 (35%) pacijentkinja, 152 (27,28%) od ukupno 557 limfnih čvorova bilo je metastatski izmenjeno na patohistolo&scaron;kom pregledu. Metastaze u limfnim čvorovima utvrđene su kod 2 pacijentkinje (7,14%) sa karcinomom vulve, 11 (39,28%) sa karcinomom cerviksa, 9 (32,14%) sa tumorima tela materice, te 6 (21,42%) sa tumorima jajnika. Od 28 pacijentkinja kod kojih su utvrđeni pozitivni limfni čvorovi, 14 pacijentkinja (50%) imalo je dobro diferentovan primarni tumor, 8 (28,57%) srednje diferentovan, dok je 6 (21,42%) imalo lo&scaron;e diferentovan primarni tumor. Od ukupno 152 metastatski izmenjena limfna čvora u na&scaron;oj studiji, 8 limfnih čvorova (5,26%) pripadalo je ingvinalnoj grupi od čega 5 (3,289%) povr&scaron;noj ingvinalnoj, a 3 ( 1,97%) dubokoj ingvinalnoj grupi, 8 (5,26%) parametrijalnoj grupi, 48 (31,58%) opturatornoj grupi, 40 (26,31%) spolja&scaron;njoj ilijačnoj grupi, 36 (23,684%) unutra&scaron;njoj ilijačnoj grupi, dok je 12 (7,89%) pripadalo zajedničkoj ilijačnoj grupi karličnih limfnih čvorova. Kraći prečnik limfnog čvora nije pokazao značajnu razliku između metastatskih ( mean &plusmn; SD, 8,3 &plusmn; 5.4 mm, raspon , 4.5-30 mm ) i limfnih čvorova koji nisu bili metastatski izmenjeni ( 6,3 mm &plusmn; 1,5 , 4,5-9,6 mm ; P= 0,191 ). Izmerena ADC vrednost bila je značajno niža kod metastatski izmenjenih limfnih čvorova (mean &plusmn; SD , ADC: 0,8725 x 10-3 mm2/s &plusmn; 0,0125) nego kod limfnih čvorova koji nisu bili metastatski izmenjeni (mean &plusmn; SD, ADC: 1,116 x 10- 3 mm2/s &plusmn; 0,1848; P=0,001). Prosečne vrednosti ADC kod b =800 s/mm2 i b =1200 s/mm2 nisu se značajno razlikovale između metastaski izmenjenih limfnih čvorova (mean &plusmn; SD, ADC: 0,8575 &plusmn; 0,0125 x 10-3 mm2/s, ADC:0,8859 &plusmn; 0,0125 x 10-3 mm2/s) i limfnih čvorova koji nisu metastatski izmenjeni (mean &plusmn; SD, ADC:1,0345 &plusmn; 0,1222 x 10-3 mm2/s, ADC:1,1125 &plusmn; 1638 x 10-3 mm2/s; P =0,657 i P = 0,877). Ako se koristi vrednost ADC od 0,860 x 10- 3 mm2 / s kao kritična vrednost za razlikovanje metastatskih od limfnih čvorova koji nisu metastatski izmenjeni, senzitivnost DWI MR iznosila je 89%, specifičnost 85% i ukupna tačnost 86%. Pozitivna prediktivna vrednost (PPV) DWI MR u detekciji limfnih metastaza u karličnoj i ingvinalnoj regiji iznosila je 30%. Negativna prediktivna vrednost (NPV) testa iznosila je 99%. Pozitivna prediktivna vrednost (PPV) MR zasnovana na kriterijumu ADC vrednosti značajno je veća u odnosu na sve kriterijuma veličine (P &lt; 0,001). Negativna prediktivna vrednost MR zasnovanoj na kriterijumima veličine limfnog čvora i na ACD vrednosti nisu se međusobno statistički značajno razlikovali (P&lt;0,05). Performanse dijagnostičke metode (MR) bile su značajno bolje za minimalnu ADC vrednost od svih kriterijuma baziranih na veličini limfnih čvorova ( P=0.001 za minimalnu ADC vrednost u odnosu na sve druge kriterijume). MRI na osnovu definisanog modela koji kombinuje kriterijum ADC vrednosti sa kriterijumom veličine ima sledeće dijagnostičke performanse za diferencijaciju malignih od benignih limfnih čvorova: senzitivnost od 95%, specifičnost 92%, sveukupna tačnost od 92,5%, pozitivnu prediktivnu vrednost od 46% i negativnu prediktivnu vrednost od 99.6%. ZAKLJUČAK: Kriterijum veličine limfnog čvora nije dovoljno precizan pokazatelj metastatske invazije limfnih čvorova. Sekvenca difuzionog kretanja (DWI) uvek se mora analizirati zajedno sa ADC mapom i visoko rezolutivnim T1 i T2 otežanim magnetnorezonantnim sekvencama. Studijom je dokazan visok stepen povezanosti između preoperativnog određivanja metastaske infiltracije karličnih i ingvinalnih limfnih čvorova malignih tumora ženskih polnih organa primenom sekvence difuzionog kretanja (DWI) i postoperativnog patohistolo&scaron;kog nalaza. Uz graničnu ADC vrednost od 0,860 x 10-3 mm2/ s, senzitivnost MRI DWI u otkrivanju metastatskih limfnih čvorova iznosi 89%, a specifičnost 85%. Kombinacija ADC vrednosti i morfolo&scaron;kih karakteristika limfnih čvorova konvencionalnim magnentno rezonantnim pregledom je najprecizniji prediktor postojanja metastatske infiltracije karličnih i ingvinalnih limfnih čvorova kod pacijentkinja sa malignim tumorima ženskih polnih organa. Tehničke karakteristike sekvenci difuzionog kretanja (DWI) u smislu razlike u visokim b vrednostima ne utiču na magnentno rezonantnu procenu metastatske infiltracije karličnih i ingvinalnih limfnih čvorova kod pacijentkinja sa malignim tumorima ženskih polnih organa. Studijom nije utvrđena statistički značajna razlika između preoperativno utvrđenih ADC vrednosti metastatski izmenjenih limfnih čvorova i stepena histolo&scaron;ke diferencijacije ovih tumora. Sekvenca difuzionog kretanja (DWI) je brza, jednostavna, neinvazivna metoda koja značajno doprinosi dijagnostičkim mogućnostima magnetne rezonance u razlikovanju benignih od malignih limfnih čvorova male karlice i ingvinuma.</p> / <p>INTRODUCTION: Malignant tumors of reproductive organs are among the leading causes of morbidity and mortality in women, both in Serbia and worldwide. Lymphatic spread is one of the most important pathways of tumor dissemination. However, conventional lymph node imaging in these patients is imprecise. Functional imaging, including diffusion-weighted magnetic resonance imaging (DWI MRI) and derived ADC map which allows quantitative analysis of diffusion parameters within a lymph node, provide promising results in discrimination benign from malignant pelvic and inguinal lymph nodes in patients with gynecological malignancies. AIM: Aim of the study was: 1. To assess diagnostic performances of DWI MRI in differentiation between benign and malignant pelvic and inguinal lymph nodes in patients with gynecological malignancies, by comparison of preoperative magnetic resonance and postoperative histopathological findings. 2. To analyze correlation between DWI characteristics of metastatic lymph nodes and grade of the primary tumor, and 3. To evaluate the influence of technical characteristics of DWI sequences on MR assessment of metastatic pelvic and inguinal lymph node and postoperative histopathological findings. MATERIAL and METHODS: The prospective clinical study was conducted in Center for Radiology, Surgery Department of Clinic for Gynecology and Obstetrics and Pathology Department of Clinical Center of Vojvodina from 2013 to 2016. It comprised 80 patients with malignant tumors of vulva, vagina, uterine cervix and body and ovaries. Based on the localization of the tumor, all patients were divided into 5 groups: group A-3 patients with vulvar cancer, group B- 1 patient with vaginal cancer, group C- 32 patients with cervical cancer, group D- 30 patients with uterine body tumors and group E- 14 patients with malignant ovarian tumors. Staging of the disease was performed after surgery based on histopathological examination of complete surgical specimen, including examination of removed lymph nodes, based on current FIGO classification separately for each primary tumor location. Preoperatively, all patients underwent MRI examination (1.5 T General Electric Signa HDx) at Center for Radiology, Clinical Center of Vojvodina. The same patients underwent standard surgical treatment according to the treatment protocol regarding the tumor type and stage, with complete pelvic and/or inguinal lymphadenectomy. Histopathological examination of surgically removed material and lymph nodes separated in pelvic and inguinal anatomic groups was performed after the surgery. RESULTS: The total of 2320 of lymph nodes were mapped and histopathologically examined in 80 patients included in the study. Metastases in lymph nodes were histopathologically confirmed in 28 patients (35%). In these 28(35%) patients, in 152 (27,28%) out of 557 lymph nodes histopathological examination confirmed metastases. Lymph node metastases were confirmed in 2 patients (7.14%) with vulvar cancer, 11 (39.28%) with cervical cancer, 9 (32.14%) with uterine body tumors and 6 (21.42%)patients with ovarian tumors. In 28 patients with positive lymph nodes, 14 patients (50%) had well differentiated primary tumor, 8 (28.57%) moderately differentiated, while 6 (21.42%) patients had poorly differentiated primary tumor. Out of 152 metastatic lymph nodes in our study, 8 lymph nodes (5.26%) were inguinal ( 5 (3.289%) superficial inguinal and 3 ( 1.97%) deep inguinal group), 8 (5.26%) were parametrial, 48 (31. 58%) obturatory, 40 (26.31%) external iliac, 36 (23.684%) internal iliac, while 12 (7. 89%) belonged to common iliac pelvic lymph nodes group. Shorter lymph node axis did not show significant difference between metastatic ( mean &plusmn; SD, 8.3 &plusmn; 5.4 mm, range , 4.5-30 mm ) and benign lymph nodes ( 6.3 mm &plusmn; 1.5 , 4.5-9.6 mm ; P= 0.191 ). Measured ADC values were significantly lower in metastatic (mean &plusmn; SD , ADC: 0.8725 x 10-3 mm2/s &plusmn; 0.0125) than benign lymph nodes (mean &plusmn; SD, ADC: 1.116 x 10-3 mm2/s &plusmn; 0.1848; P=0.001). Mean ADC values at b =800 s/mm2 and b =1200 s/mm2 did not differ significantly between metastatic (mean &plusmn; SD, ADC: 0.8575 &plusmn; 0.0125 x 10-3 mm2/s, ADC:0.8859 &plusmn; 0,0125 x 10-3 mm2/s) and benign lymph nodes (mean &plusmn; SD, ADC:1.0345 &plusmn; 0.1222 x 10-3 mm2/s, ADC:1.1125 &plusmn; 1638 x 10-3 mm2/s; P =0.657 i P = 0.877). If ADC value of 0.860 x 10- 3 mm2 / s is determined as a cut off value for discrimination of benign and malignant lymph nodes, DWI MRI sensitivity was 89%, specificity 85% and overall accuracy was 86%. Positive predictive value (PPV) of DWI MR in detection of pelvic and inguinal lymph node metastases was 30%. Negative predictive value (NPV) of the test was 99%. MRI PPV based on ADC value criteria was significantly higher compared to all size-based criteria (P &lt; 0,001). MRI NPV based on size based and ADC values criteria did not differ significantly (P&lt;0,05). Performances of diagnostic method (MRI) were significantly better for minimal ADC value compared to all lymph node size-based criteria ( P=0.001 for minimal ADC value compared to all other criteria). Combination of ADC value criteria and size-based criteria yields MRI the following diagnostic performances in discrimination between benign and malignant lymph nodes: sensitivity 95%, specificity 92%, overall accuracy 92.5%, positive predictive value 46% and negative predictive value 99.6%. CONCLUSION: Lymph node size is not sufficiently precise criteria for determination of metastatic lymph node involvement. DWI sequence always needs to be evaluated together with ADC map and high resolution T1W and T2W magnetic resonance sequences. The study shows high correlation between preoperative assessment of pelvic and inguinal lymph node metastases from gynecological malignancies using MRI DWI and postoperative histopathological findings. With a cut off ADC value of 0.860 x 10-3 mm2/ s, sensitivity of MRI DWI in metastatic lymph node detection is 89%, while specificity is 85%. Combination of ADC values and morphological lymph nodes characteristics assessed by conventional MRI is the most precise predictor of metastatic pelvic and inguinal lymph node invasion in patients with gynecological malignancies. Technical characteristics of DWI i.e. different high b-values do not influence MR assessment of metastatic pelvic and inguinal lymph node involvement in patients with gynecological malignancies. The study did not confirm statistically significant difference between preoperatively measured ADC valued of metastatic lymph nodes and histological grade of primary tumors. DWI MRI sequence is fast, simple, noninvasive method which aids significantly to MRI diagnostic performances in discrimination between benign and malignant pelvic and inguinal lymph nodes.</p>

Dopamine is an important neurotransmitter that is involved in several human functions such as reward, cognition, emotions and movement. Abnormalities of the neurotransmitter itself, or the dopamine receptors through which it exerts its actions, contribute to a wide range of psychiatric and neurological disorders such as Parkinson’s disease and schizophrenia. Thus far, despite the great interest and extensive research, the exact role of dopamine and the causalities of dopamine related disorders are not fully understood. Here we have developed multimodal imaging methods, to investigate the release of dopamine and the distribution of the dopamine D2-like receptor family in-vivo in healthy humans. We use the [¹¹C]PHNO PET ligand, which enables exploration of dopamine-related parameters in striatal regions, and for the first time in extrastriatal regions, that are known to be associated with distinctive functions and disorders. Our methods involve robust approaches for the manual and automated delineation of these brain regions, in terms of structural and functional organisation, using information from structural and diffusion MRI images. These data have been combined with [¹¹C]PHNO PET data for quantitative dopamine imaging. Our investigation has revealed the distribution and the relative density of the D3R and D2R sites of the dopamine D2-like receptor family, in healthy humans. In addition, we have demonstrated that the release of dopamine has a functional rather than a structural specificity and that the relative densities of the D3R and D2R sites do not drive this specificity. We have also shown that the dopamine D3R receptor is primarily distributed in regions that have a central role in reward and addiction. A finding that supports theories that assigns a primarily limbic role to the D3R.

<p>Uvod: Dijabetes melitus (DM) je oboljenje koje poprima karakteristike globalne epidemije. Sve ţe&scaron;&scaron;e oboljevaju pacijenti mlaŤeg ţivotnog doba. Simptomi DM tip 2 su blagi, ţesto neprimetni, te se oboljenje otkriva kada se ve&scaron; manifestuju komplikacije. Dijabetesna nefropatija (DN) je jedna od mnogobrojnih komplikacija dijabetes melitusa tip 2, koja se zavr&scaron;ava terminalnom bubreţnom insuficijencijom. DN se ţesto neblagovremeno dijagnostikuje, zbog ţega se kasno zapoţinje leţenje. Rano otkrivanje DN od kljuţnog je znaţaja, jer omogu&scaron;ava primenu terapijskih postupaka usmerenih na oţuvanje preostalih zdravih nefrona i prevenciju terminalne bubreţne slabosti. Cilj: Prikazati poreme&scaron;aj difuzije molekula vode unutar bubrega kod DN, kori&scaron;&scaron;enjem mapa prividnog koeficijenta difuzije, kvantifikacijom vrednosti prividnog koeficijenta difuzije (ADC) i frakcione anizotropije (FA). Materijal i metode: U prospektivnu studiju bilo je ukljuţeno 10 zdravih dobrovoljaca i 91 pacijent oboleo od DM tip 2. Pacijenti oboleli od DM tip 2 podeljeni su u ţetiri grupe na osnovu vrednosti procenjene jaţine glomerularne filtracije (JGF) (grupe: I JGF &ge; 90, II 89-60, III 59-30, IV &le; 29 ml/min/1,73m&sup2;). Svim ispitanicima uraŤen je MR pregled bubrega, uz primenu DWI (b=0 i b=400 s/mm&sup2;) i DTI (b=1000 s/mm&sup2;) sekvence, na aparatu jaţine 1.5T. ADC i FA vrednosti raţunate su u &scaron;est regija od interasa, po tri u korteksu i meduli svakog bubrega. Dobijene vrednosti komparirane su sa laboratorijskim parametrima bubreţne funkcije (urea, kreatinin, mokra&scaron;na kiselina) i procenjenom JGF. Rezultati: Ne postoje statistiţki znaţajne razlike ADC i FA vrednosti parenhima, korteksa i medule levog i desnog bubrega kod zdravih dobrovoljaca i DM pacijenata. Kod DM pacijenata ADC je ve&scaron;a u korteksu nego u meduli (p=0,00), a FA vrednost je ve&scaron;a u meduli nego u korteksu (p=0,284). Urea, kreatinin i cistatin C imaju negativnu korelaciju sa ADC korteksa, medule i parenhima (p&lt;0,05), a JGF ima pozitivnu korelaciju sa ADC korteksa, medule i parenhima, kao i sa FA medule (p&lt;0,05) kod DM pacijenata. Na osnovu Post hoc testa za ADC, kod DM pacijenata postoje razlike izmeŤu I i IV grupe, izmeŤu II i IV grupe i III i IV grupe (p&le;0,05). IzmeŤu godina ţivota, teţine, BMI, JGF, HbA1c, uree i &Scaron;UK-a, postoji razlika DM pacijenata i zdravih dobrovoljaca (p&lt;0,05). Niţa je vrednost FA medule DM pacijenata u odnosu na zdrave dobrovoljce (p&lt;0,05). Postoji razlika ADC korteksa, medule i parenhima izmeŤu zdravih dobrovoljaca i DM pacijenata IV grupe, kao izmeŤu DM pacijenata I i II grupe u odnosu na IV grupu. TakoŤe postoji razlika izmeŤu FA medule zdravih dobrovoljaca i DM pacijenata I i IV grupe (p&lt;0,05). Regresiona analiza pokazala je uticaj kreatinina na ADC desnog bubrega i ADC oba bubrega, dok procenjena JGF i cistatin C imaju uticaj na ADC desnog i levog bubrega, ADC oba bubrega i FA levog bubrega (p&lt;0,05). Traktografija je prikazala naru&scaron;enu arhitektoniku kod pacijenata sa o&scaron;te&scaron;enom bubreţnom funkcijom. Zakljuţak: Postoji korelacija laboratorijskih parametara bubreţne funkcije i procenjene JGF sa ADC i FA vrednostima bubrega, &scaron;to ukazuje na ulogu funkcionalnog magnetno rezonantnog imidţinga u dijagnostici dijabetesne nefropatije. Neophodna su dalja istraţivanja koja &scaron;e doprineti standardizaciji MR protokola i potvrdi znaţaja MR biomarkera u dijagnostici DN. Na osnovu na&scaron;ih rezultata vrednost FA medule osetljiviji je parametar od ADC vrednosti u otkrivanju ranog o&scaron;te&scaron;enja bubrega u sklopu dijabetes melitusa.</p> / <p>Introduction: Diabetes mellitus (DM) is a disease that takes on the characteristics of a global epidemic. Patients of younger age are more and more commonly affected. Symptoms of type 2 DM are mild, often imperceptible, and therefore the disease is usually detected when complications are already manifested. Diabetic nephropathy (DN) is one of the many complications of type 2 diabetes mellitus that leads to terminal renal failure. Diagnosis of DN is often late, causing the delay of the treatmen. Early detection of DN is crucial because it allows the application of therapeutic procedures aimed at preserving the remaining healthy nephrons and preventing terminal renal failure. Objective: To investigate a diffusion of water molecule within a kidney in DN using apparent diffusion coefficient maps, by quantification of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in diabetic patients with DM type 2. Material and methods: The prospective study comprised 10 healthy volunteers and 91 DM type 2 patients. DM patients were divided into four groups based on the values of the estimated glomerular filtration (eGFR) (groups: I eGFR &ge; 90, II 89-60, III 59-30, IV &le; 29 ml/min/1.73m&sup2;). All subjects were scanned by 1.5T MR using DWI (b=0 and b=400 s/mm&sup2;) and DTI (b=1000 s/mm&sup2;) sequences. ADC and FA values were calculated in six regions of interest, three in cortex and three in medulla of each kidney. Obtaned values were compared to laboratory parameters of renal function (urea, creatinine, uric acid) and eGFR. Results: There were no statistically significant differences between ADC and FA values of parenchyma, cortex and medulla of the left and the right kidney in healthy volunteers and DM patients. In DM patients, the ADC value was higher in the cortex than in the medulla (p=0.00) and the FA value was higher in the medulla than in the cortex (p=0.284). The negative correlation was found between urea, creatinine and cystatin C with ADC cortex, medulla and parenchyma (p&lt;0.05), and the eGFR was positively correlated with ADC cortex, medulla and parenchyma, and with FA medulla (p&lt;0.05) in DM patients. Based on the Post hoc test for ADC, in DM patients there were differences between I and IV group, between II and IV group, III and IV group (p&le;0,05). Regarding age, weight, BMI, GFR, HbA1c, urea, and glucose in the serum, there was a difference between DM patients and healthy volunteers (p&lt;0.05). The FA of medulla in DM patients was lower than of healthy volunteers (p&lt;0.05). There were differences in ADC of cortex, medulla, and parenchyma between healthy volunteers and DM patients of IV group, as well as between DM patients of I and II group compared to IV group. There were differences of medulla FA values between healthy volunteers and group I, accompanied by healthy and IV group of DM patients (p&lt;0.05). Regression analysis showed the influence of creatinine on ADC of right kidney and ADC of both kidneys, while eGFR and cystatin C have an effect on ADC of right and left kidney, ADC of both kidneys and FA of left kidney (p&lt;0.05). The tractography showed the disturbed architectonics in patients with impaired renal function. Conclusion: There is correlation of laboratory parameters of renal function and eGFR with ADC and FA values of the kidney, indicating the role of functional magnetic resonance imaging in the diagnosis of DN. Further research that will contribute to standardizing the MR protocol and confirming the importance of MRI biomarker in the diagnosis of DN are needed. Based on our results, the values of medulla FA is more sensitive parameter than the ADC value in detecting early kidney damage in the context of diabetes mellitus.</p>

INTRODUÇÃO: O transtorno de déficit de atenção com hiperatividade (TDAH) persistente em adultos apresenta prevalência significativa na população geral. Nota-se também uma alta taxa de comorbidade com outros quadros psiquiátricos, especialmente o transtorno bipolar (TB). Entretanto, ainda hoje discutem-se as próprias definições do TDAH e os limites da comorbidade TDAH+TB, que poderia ser uma extensão dos sintomas do espectro bipolar, uma sobreposição dos dois transtornos ou uma entidade separada com substrato neurobiológico distinto. Impõe-se, assim, a pesquisa de biomarcadores válidos com potencial aplicação na prática clínica. O surgimento recente de técnicas de classificação de padrões morfológicos cerebrais complexos possibilita uma investigação mais direcionada de biomarcadores, buscando em cada indivíduo um conjunto de características que seja capaz de classificá-lo como pertencente a um determinado grupo. OBJETIVOS: Aplicar, de maneira inédita, a técnica de reconhecimento automatizado de padrão aos dados de neuroimagem de pacientes adultos sem tratamento prévio com diagnóstico de TDAH com início na infância, TB, TDAH+TB e controles saudáveis (CS), em busca de assinaturas neuroanatômicas associadas a estes transtornos. MÉTODOS: Três grupos de adultos nunca tratados compostos de 67 sujeitos com TDAH, 30 sujeitos com TB e 16 sujeitos preenchendo critérios diagnósticos para ambos os transtornos; e uma amostra de CS (n=66), foram submetidos ao exame de ressonância magnética (RM) estrutural e de imagem por tensor de difusão (diffusion tensor imaging; DTI). Através de um método automatizado, regiões de interesse foram posicionadas ao longo de todo o cérebro e através destas foram obtidas medidas cerebrais a partir das imagens multimodais. Tais medidas foram usadas como dados de entrada para um classificador não-linear baseado em support vector machine (SVM). Comparações entre todos os pacientes e CS foram feitas através de subgrupos pareados individualmente para gênero e idade e pareados entre os grupos para nível socioeconômico e escolaridade. As medidas de desempenho diagnóstico foram analisadas com o auxílio de curvas receiver operating characteristic (ROC). RESULTADOS: As análises de classificação entre todos os subgrupos apresentaram resultados expressivamente acima do acaso, com exceção da comparação entre os pacientes com TB e os CS (p=0,09). A comparação entre os subgrupos com TDAH e CS apresentou medidas de área sob a curva (AUC) e acurácia diagnóstica de até 0,71 e 66,2% (p=0,003). A comparação entre os subgrupos com TDAH e TB obteve AUC e acurácia diagnóstica de até 0,78 e 70,2% (p=0,01). As análises de classificação entre os pacientes TDAH+TB e todos os outros subgrupos resultaram em valores de até 0,89 e 80,5% (p=0,0009) de AUC e acurácia diagnóstica respectivamente. CONCLUSÃO: Os resultados fornecem endosso neurobiológico para a validade do diagnóstico clinico de TDAH em adultos. As características cerebrais mostraram-se suficientemente fortes para o diagnóstico diferencial entre o TDAH e o TB e também reforçam a hipótese de que a associação TDAH+TB deve ser compreendida como uma entidade neurobiológica distinta. Restam ainda relevantes dificuldades na busca de biomarcadores para a caracterização do TB. As assinaturas neuroanatômicas identificadas neste estudo podem fornecer informações objetivas adicionais e valiosas, servindo como base para estudos futuros que avaliem sua possível influência em decisões terapêuticas dos pacientes apresentando sintomas do espectro TDAH e da comorbidade TDAH+TB / INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition in the general adult population. Also important is its high rate of comorbidity with other psychiatric disorders, particularly bipolar disorder (BD). However, not only the definition of ADHD is still a matter of discussion but also the limits of the ADHD+BD comorbidity; such comorbidity may be interpreted as a continuum spectrum of BD, an overlap of symptoms, or a separate diagnostic entity with a distinct neurobiological substrate. Therefore, further search for valid biomarkers with potential application in clinical practice is still required. The recent development of high-dimensional pattern recognition techniques has allowed targeted investigations of biomarkers, searching for sets of characteristics that could be used to classify each patient in a particular group. OBECTIVES: To apply, for the first time in the literature, machine learning-based pattern recognition methods to neuroimaging data obtained in never-treated adults with childhood-onset ADHD, BD, ADHD+BD and healthy controls (HC), searching for different neuroanatomical signatures associated with each disorder. METHODS: Three groups of never treated adults as following: 67 ADHD patients, 30 BD patients, 16 patients fulfilling diagnostic criteria for both disorders; and a sample of HC (n=66) underwent structural magnetic resonance imaging (MRI) and diffusion magnetic resonance imaging (DTI) acquisitions. A support vector machine (SVM) classifier with non-linear kernel was applied on multi-modal image features extracted on regions-of-interest placed across the whole brain. Comparisons among all patients and controls were carried out through subgroups individually matched for gender and age, and group-matched for years of education and socio-economic status. Diagnostic performance measures were evaluated by computing receiver operating characteristic (ROC) curves. RESULTS: All results on classification analyses were clearly significant above chance level, except in the comparison analysis between BD patients and HC (p=0.09). The comparison between ADHD and HC subgroups afforded area under the curve (AUC) measures and diagnostic accuracy of up to 0.71 and 66.2% (p=0.003). Comparison between ADHD and BD subgroups achieved AUC and diagnostic accuracy of up to 0.78 and 70.2% (p=0.01). Classification analysis between ADHD+BD patients and the other subgroups yielded AUC and diagnostic accuracy values of up to 0.89 and 80.5% (p=0.0009). CONCLUSION: The present study provides neurobiological endorsement to the validity of the clinically-based diagnosis of ADHD in adults. Brain features were strong enough to the differential diagnosis between ADHD and BD, as well as to reinforce the hypothesis that ADHD+BD may represent a distinct neurobiological entity. However, relevant challenges persist regarding the search for biomarkers for BD. The neuroanatomical signatures identified herein may provide additional, objective information, paving the way for future studies assessing its influence in treatment decisions in adults with ADHD and ADHD+BD spectrum symptoms

INTRODUÇÃO: O transtorno de déficit de atenção com hiperatividade (TDAH) persistente em adultos apresenta prevalência significativa na população geral. Nota-se também uma alta taxa de comorbidade com outros quadros psiquiátricos, especialmente o transtorno bipolar (TB). Entretanto, ainda hoje discutem-se as próprias definições do TDAH e os limites da comorbidade TDAH+TB, que poderia ser uma extensão dos sintomas do espectro bipolar, uma sobreposição dos dois transtornos ou uma entidade separada com substrato neurobiológico distinto. Impõe-se, assim, a pesquisa de biomarcadores válidos com potencial aplicação na prática clínica. O surgimento recente de técnicas de classificação de padrões morfológicos cerebrais complexos possibilita uma investigação mais direcionada de biomarcadores, buscando em cada indivíduo um conjunto de características que seja capaz de classificá-lo como pertencente a um determinado grupo. OBJETIVOS: Aplicar, de maneira inédita, a técnica de reconhecimento automatizado de padrão aos dados de neuroimagem de pacientes adultos sem tratamento prévio com diagnóstico de TDAH com início na infância, TB, TDAH+TB e controles saudáveis (CS), em busca de assinaturas neuroanatômicas associadas a estes transtornos. MÉTODOS: Três grupos de adultos nunca tratados compostos de 67 sujeitos com TDAH, 30 sujeitos com TB e 16 sujeitos preenchendo critérios diagnósticos para ambos os transtornos; e uma amostra de CS (n=66), foram submetidos ao exame de ressonância magnética (RM) estrutural e de imagem por tensor de difusão (diffusion tensor imaging; DTI). Através de um método automatizado, regiões de interesse foram posicionadas ao longo de todo o cérebro e através destas foram obtidas medidas cerebrais a partir das imagens multimodais. Tais medidas foram usadas como dados de entrada para um classificador não-linear baseado em support vector machine (SVM). Comparações entre todos os pacientes e CS foram feitas através de subgrupos pareados individualmente para gênero e idade e pareados entre os grupos para nível socioeconômico e escolaridade. As medidas de desempenho diagnóstico foram analisadas com o auxílio de curvas receiver operating characteristic (ROC). RESULTADOS: As análises de classificação entre todos os subgrupos apresentaram resultados expressivamente acima do acaso, com exceção da comparação entre os pacientes com TB e os CS (p=0,09). A comparação entre os subgrupos com TDAH e CS apresentou medidas de área sob a curva (AUC) e acurácia diagnóstica de até 0,71 e 66,2% (p=0,003). A comparação entre os subgrupos com TDAH e TB obteve AUC e acurácia diagnóstica de até 0,78 e 70,2% (p=0,01). As análises de classificação entre os pacientes TDAH+TB e todos os outros subgrupos resultaram em valores de até 0,89 e 80,5% (p=0,0009) de AUC e acurácia diagnóstica respectivamente. CONCLUSÃO: Os resultados fornecem endosso neurobiológico para a validade do diagnóstico clinico de TDAH em adultos. As características cerebrais mostraram-se suficientemente fortes para o diagnóstico diferencial entre o TDAH e o TB e também reforçam a hipótese de que a associação TDAH+TB deve ser compreendida como uma entidade neurobiológica distinta. Restam ainda relevantes dificuldades na busca de biomarcadores para a caracterização do TB. As assinaturas neuroanatômicas identificadas neste estudo podem fornecer informações objetivas adicionais e valiosas, servindo como base para estudos futuros que avaliem sua possível influência em decisões terapêuticas dos pacientes apresentando sintomas do espectro TDAH e da comorbidade TDAH+TB / INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition in the general adult population. Also important is its high rate of comorbidity with other psychiatric disorders, particularly bipolar disorder (BD). However, not only the definition of ADHD is still a matter of discussion but also the limits of the ADHD+BD comorbidity; such comorbidity may be interpreted as a continuum spectrum of BD, an overlap of symptoms, or a separate diagnostic entity with a distinct neurobiological substrate. Therefore, further search for valid biomarkers with potential application in clinical practice is still required. The recent development of high-dimensional pattern recognition techniques has allowed targeted investigations of biomarkers, searching for sets of characteristics that could be used to classify each patient in a particular group. OBECTIVES: To apply, for the first time in the literature, machine learning-based pattern recognition methods to neuroimaging data obtained in never-treated adults with childhood-onset ADHD, BD, ADHD+BD and healthy controls (HC), searching for different neuroanatomical signatures associated with each disorder. METHODS: Three groups of never treated adults as following: 67 ADHD patients, 30 BD patients, 16 patients fulfilling diagnostic criteria for both disorders; and a sample of HC (n=66) underwent structural magnetic resonance imaging (MRI) and diffusion magnetic resonance imaging (DTI) acquisitions. A support vector machine (SVM) classifier with non-linear kernel was applied on multi-modal image features extracted on regions-of-interest placed across the whole brain. Comparisons among all patients and controls were carried out through subgroups individually matched for gender and age, and group-matched for years of education and socio-economic status. Diagnostic performance measures were evaluated by computing receiver operating characteristic (ROC) curves. RESULTS: All results on classification analyses were clearly significant above chance level, except in the comparison analysis between BD patients and HC (p=0.09). The comparison between ADHD and HC subgroups afforded area under the curve (AUC) measures and diagnostic accuracy of up to 0.71 and 66.2% (p=0.003). Comparison between ADHD and BD subgroups achieved AUC and diagnostic accuracy of up to 0.78 and 70.2% (p=0.01). Classification analysis between ADHD+BD patients and the other subgroups yielded AUC and diagnostic accuracy values of up to 0.89 and 80.5% (p=0.0009). CONCLUSION: The present study provides neurobiological endorsement to the validity of the clinically-based diagnosis of ADHD in adults. Brain features were strong enough to the differential diagnosis between ADHD and BD, as well as to reinforce the hypothesis that ADHD+BD may represent a distinct neurobiological entity. However, relevant challenges persist regarding the search for biomarkers for BD. The neuroanatomical signatures identified herein may provide additional, objective information, paving the way for future studies assessing its influence in treatment decisions in adults with ADHD and ADHD+BD spectrum symptoms

Objectives: To compare 64-slice contrast-enhanced computed tomography (CT) with 3-Tesla magnetic resonance imaging (MRI) using Gd-EOB-DTPA for the diagnosis of hepatocellular carcinoma (HCC) and evaluate the utility of diffusion-weighted imaging (DWI) in this setting. Methods: 3-phase-liver-CT was performed in fifty patients (42 male, 8 female) with suspected or proven HCC. The patients were subjected to a 3-Tesla-MRI-examination with Gd-EOB-DTPA and diffusion weighted imaging (DWI) at b-values of 0, 50 and 400 s/mm2. The apparent diffusion coefficient (ADC)-value was determined for each lesion detected in DWI. The histopathological report after resection or biopsy of a lesion served as the gold standard, and a surrogate of follow-up or complementary imaging techniques in combination with clinical and paraclinical parameters was used in unresected lesions. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were evaluated for each technique. Results: MRI detected slightly more lesions that were considered suspicious for HCC per patient compared to CT (2.7 versus 2.3, respectively). ADC-measurements in HCC showed notably heterogeneous values with a median of 1.2±0.5×10−3 mm2/s (range from 0.07±0.1 to 3.0±0.1×10−3 mm2/s). MRI showed similar diagnostic accuracy, sensitivity, and positive and negative predictive values compared to CT (AUC 0.837, sensitivity 92%, PPV 80% and NPV 90% for MRI vs. AUC 0.798, sensitivity 85%, PPV 79% and NPV 82% for CT; not significant). Specificity was 75% for both techniques. Conclusions: Our study did not show a statistically significant difference in detection in detection of HCC between MRI and CT. Gd-EOB-DTPA-enhanced MRI tended to detect more lesions per patient compared to contrast-enhanced CT; therefore, we would recommend this modality as the first-choice imaging method for the detection of HCC and therapeutic decisions. However, contrast-enhanced CT was not inferior in our study, so that it can be a useful image modality for follow-up examinations.

<p>Alchajmerova bolest je najče&scaron;ća demencija od svih demencija i karakteri&scaron;e je depozicija senilinih plakova i neurofibrilarnih klubadi u kortikalnim moždanim regionima, koje daljim razvojem bolesti postaju atrofične. Klinički se karakteri&scaron;e smetnjma na planu pamćenja, egzekutivnih funkcija, pažnje i ostalih kognitivnih funkcija uz odustsvo sposobnosti samostalnog funkcionisanja u svakodnevnom životu. Blagi kognitivni poremeća (BKP) je klinički entitet koji se smatra početnim stadijumom demencije u kom se registruju smetnje na planu pamćenja, ali i drugih kognitvnih funkcija, uz očuvanu funkcionalnost u svakodnevnom životu. Kod obe bolesti je utvrđeno da pored kortikalnog zahvatanja, patolo&scaron;kim procesom je zahvaćena i bela masa mozga. U dana&scaron;nje vreme se mirkostrukturno o&scaron;tećenje bele mase mozga može ispitati difuzionim tenzorskim imidžinogom (DTI) na magnentoj rezonanci mozga (MR). Cilj: Utvrditi razlike neuropsiholo&scaron;kih skorova i razlike DTI parametara između obolelih od AB, BKP i kontrolne grupe zdravih ispitanika, kao i utvrditi da li postoji korelacija između neuropsiholo&scaron;kih skorova i DTI parametara kod BKP i AB.&nbsp; Metode: U istraživanje je uključeno tri ispitivane grupe od po 30 ispitanika: oboleli od AB u blagom stadijumu bolesti, oboleli od amnestičkog multi-domen BKP i kontrolna grupa zdravih ispitanika. Dijagnoza kod obolelih u obe grupe je postavljena na osnovu kliničkih kriterijuma aktuelnih dijagnostičkih kriterijuma iz 2011. godine. Kod svih ispitanika je sprovedeno detaljno neuropsiholo&scaron;ko testiranje u cilju procene kognitivnih funkcija (smetnji na planu pamćenja, egzekutivnih funkcija, pažnje, govora, vizuospacijalnih i vizuokonstrukcionih sposobnosti), depresivnosti i drugih neuropsihijatrijskih simptoma i kvaliteta života. Samo je kod obolelih od AB dopunski vr&scaron;ena procena sposobnosti svakodnevnog funkcionisanja. Kognitivne funkcije su ispitane formiranjem kognitivnih domena, na osnovu pretpostavke o zajedničkom predmetu merenja kori&scaron;ćenih testova. Potom je načinjen MR mozga, u okviru koje je analiziran i DTI. Dalja obrada DTI je sprovedena primenom TBSS metode, čime su dobijene vrednosti DTI parametara: frakcione anizotropije (FA), srednje difuzivnosti (SD), radijalne difuzivnosti (RD) i aksijalne difuzivnosti (DA). Nakon toga je načinjena korelacija neuropsiholo&scaron;kog postignuća i DTI parametara kori&scaron;ćenjem Pirsonovog, odnosno Spirmanovog koeficijenta korelacije. Rezultati: Oboleli od AB su imali lo&scaron;ije postignuće na planu vizuelnog pamćenja, verbalnog pamćenja, neposrednog upamćivanja, odloženog prisećanja, pažnje, govora, egzekutivnih funkcija, mi&scaron;ljenja, radne memorije i vizuospacijalnih i vizuokonstrukcionih sposobnosti u odnosu na kontrolnu grupu zdravih. Oboleli od BKP su imali lo&scaron;ije postignuće u odnosu na kontrolnu grupu zdravih u domenima vizuelno pamćenje, neposredno upamćivanje, odloženo prisećanje, govor, mi&scaron;ljenje i vizuospacijalne i vizuokonstrukcione sposobnosti. Obe grupe obolelih su ispoljile vi&scaron;e depresivnih simptoma u odnosu na kontrolnu grupu zdravih ispitanika. Takođe, obe grupe obolelih ispoljavaju statistički značajno vi&scaron;e neuropsihijatrijskih simptoma u odnosu na zdrave ispitanike, gde se kod obolelih od AB registruju sumanute ideje, halucinacije, agitacija, euforija, dezinhibicija, ritabilnost i apatija, dok se kod obolelih od BKP registruju anksioznost i iritabilnost. Oboleli od AB imaju lo&scaron;iji kvalitet života u odnosu na zdrave ispitanike, dok između oboleli od BKP i zdravih ispitanika nema razlike u proceni kvaliteta života. &Scaron;to se tiče DTI parametara, oboleli od AB imaju niži FA i vi&scaron;u SD, RD i DA u odnosu na zdrave ispitanike na vi&scaron;e puteva bele mase: prednji krak kapsule interne, prednja korona radijata, telo korpusa kalozuma, cingulum, kapsula eksterna, fornix-strija terminalis, koleno korpusa kalozuma, donji fronto-okcipitalni fascikulus, zadnja korona radijata, gornji fronto-okcipitalni fascikulus, gornji longitudinalni fascikulus i fascikulus uncinatus. Oboleli od BKP imaju sniženu FA i povi&scaron;enu SD, RD i DA u regiji forniksa u odnosu na zdrave ispitanike. Kod obolelih od AB registrovane su značajne povezanosti mikrostrukturnog o&scaron;tećenja bele mase i o&scaron;tećenja svih kognitivnih domena, izuzev domena mi&scaron;ljenje, dok su kod obolelih od BKP registrovane značajne povezanosti mikrostrukturnog o&scaron;tećenja bele mase i o&scaron;tećenja svih kognitivnih domena, izuzev domena egzekutivne funkcije. U grupi obolelih od BKP je bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena verbalno pamćenje, odloženo prisećanje i govor sa o&scaron;tećenjem bele mase mozga, dok je kod AB bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena vizuelno pamćenje, neposredno upamćivanje, pažnja, radna memorija i vizuospacijalne i vizuokontrukcione sposobnosti sa o&scaron;tećenjem bele mase mozga. Depresivnost je jedino u grupi BKP značajno korelirala sa o&scaron;tećenjem određenih puteva bele mase mozga. Zaključak: U blagom stadijumu obolelih od AB se registruje kognitivno o&scaron;tećenje svih ispitivanih domena, vi&scaron;e su ispoljeni depresivni simptomi, utvrđen je veliki broj neuropsihijatrijskih simptoma i naru&scaron;en je kvalitet života u odnosu na zdrave ispitanike. Kod obolelih od BKP je registrovano kognitivno o&scaron;tećenje vi&scaron;e od pola procenjivanih kognitivnih funkcija, vi&scaron;e su ispoljeni depresivni simptomi i utvrđeno prisustvo anksioznosti i iritabilnosti, dok kvalitet života nije naru&scaron;en u ovoj fazi bolesti u odnosu na zdrave ispitanike. Rezultati vezani za mikrostrukturno o&scaron;tećenja mozga u najranijim fazama AB ukazuju da je neuronska mreža značajno o&scaron;tećena u najranijim kliničkim fazama bolesti, dok je u stadijumu BKP izolovana na o&scaron;tećenje u regiji forniksa. U grupi obolelih od BKP je bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena verbalno pamćenje, odloženo prisećanje i govor sa o&scaron;tećenjem bele mase mozga, dok je kod AB bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena vizuelno pamćenje, neposredno upamćivanje, pažnja, radna memorija i vizuospacijalne i vizuokontrukcione sposobnosti sa o&scaron;tećenjem bele mase mozga. Stepen depresivnosti i o&scaron;tećenje bele mase mozga je povezano isključivo na nivou BKP.</p> / <p>Alzheimer&#39;s disease (AD) is the most common dementia of all dementia with deposition of senile plaques and neurofibrillary tangles in cortical brain regions, which become atrophic in the further disease development. It`s main clinical characteristics are impairment of memory, executive function, attention and other cognitive functions with impairment in daily living activities. Mild cognitive impairment (MCI) is a clinical entity considered as an initial stage of dementia with present memory impairment, as well as other cognitive functions, while maintaining the functionality of the everyday life. In both diseases, pathological processes affect also the white matter of the brain. Nowadays, microstructural damage of the brain white matter is diagnosed by using diffusion tensor imaging (DTI) in the brain magnetic resonance imaging (MR). Objective: The aim of this study was to determine differences in neuropsychological scores and differences in DTI parameters between patients with AD, MCI and control groups of healthy subjects, as well as to determine whether there is a correlation between scores and DTI parameters in MCI and AD.&nbsp; Methods: The study included three groups of 30 patients each: of AD patients in the mild stage of the disease, patients with multi-domain amnestic MCI, and healthy controls. The patient&rsquo;s diagnosis are based upon clinical criteria of current diagnostic criteria proposed in 2011. All patients had assessment of cognitive functions (impairment of memory, executive function, attention, language, visuospatial and construction abilities), depressive symptoms and other behavioral disorders and quality of life. Only in patients with AD, we also assessed ability of daily living activities. Cognitive functions were tested by forming cognitive domains, based on the assumption of a common object of measurement of analyzed tests. Further, participants had MRI scan, in which DTI was analyzed. DTI post-processing was carried out by using TBSS method, whereby the values of DTI parameters were: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (DA). We conducted correlation analysis of the neuropsychological achievements and DTI parameters using Pearson or Spearman&rsquo;s correlation coefficient, dependent on variable distribution. Results: The patients with AD had lower scores in the field of visual memory, verbal memory, immediate and delayed recall, attention, language, executive functions, reasoning, working memory and visuospatial and construction abilities compared to the control group. Patients with MCI had lower scores compared to the control group in the domains of visual memory, immediate and delayed recall, language, reasoning, and visuospatial and construction abilities. Both groups of patients have more depressive symptoms in relation to the control group of healthy subjects. In addition, both groups of patients exhibited a significantly higher degree of behavioral disorders as compared to healthy subjects, where AD patients experienced delusions, hallucinations, agitation, euphoria, disinhibition, irritability and apathy, while MCI patients experienced anxiety and irritability. Patients with AD had a poor quality of life compared to healthy subjects, whereas people with MCI did not. As for the parameters of DTI, AD patients had decrease of FA and increase of MD, RD, and DA compared to the healthy subjects in the multiple white matter tracts: anterior limb of internal capsule, anterior part of corona radiata, the body of the corpus callosum, cingulum, external capsule, fornix- striae terminalis, genu of the corpus callosum, inferior frontal-occipital fasciculus, posterior corona radiata, superior frontal-occipital fasciculus, superior longitudinal fasciculus and fasciculus uncinatus. Patients with MCI had decreased FA and increased MD, RD and DA in the fornix compared to healthy subjects. In AD patients, there was significant association between microstructural white matter brain damage and all cognitive domains, except domain reasoning, while in patients with MCI significant association was evident between microstructural white matter damage and all cognitive domains, except the domain of executive function. Results related to the microstructural white matter brain damage in mild AD indicates that wide neural network is significantly damaged at the earliest clinical stages of the disease, while in MCI stage only fornix shows microstructural white matter brain damage. Level of impairment of verbal memory, delayed recall and language correlates more frequently in MCI group compared to mild AD group, where impairment in the field of visual memory, immediate recall, attention, working memory and visuospatial and construction abilities correlates more frequently with white matter brain damage. Association of depressive symptoms and white matter brain damage was significant in MCI patients. Conclusion: In mild AD, cognitive impairment is present in all cognitive domains; patients experience more depressive symptoms and wider spectrum of behavioral disorders with compromised quality of life compared to healthy subjects. In MCI patients, cognitive impairment is present in more than half of the assessed cognitive functions; patients also experience more depressive symptoms, as well as anxiety and irritability without quality of life deterioration compared to healthy subjects. Results related to the microstructural white matter brain damage in mild AD indicates that wide neural network is significantly damaged at the earliest clinical stages of the disease, while in MCI stage only fornix shows microstructural white matter brain damage. Level of impairment of verbal memory, delayed recall and language correlates more frequently in MCI group compared to mild AD group, where impairment in the field of visual memory, immediate recall, attention, working memory and visuospatial and construction abilities correlates more frequently with white matter brain damage. The degree of depression correlated significantly with white matter brain damage solely at the level of MCI.</p>