Optimization of activity level in rCBF SPECT using the observer study Visual Grading Regression

The purpose of this work is to assess the activity level needed to achieve satisfactory diagnostic information in regional cerebral blood flow single photon emission computed tomography (rCBF SPECT) by introducing a new evaluation method to be used for and hopefully facilitate optimization studies in nuclear medicine in the future. The purpose is further to perform a visual grading study and investigate the use of this new evaluation method, Visual Grading Regression (VGR). Image quality criteria applicable to rCBF SPECT images will be defined in this work and their relevance for evaluating rCBF SPECT image quality is investigated. The study comprises a material of 21 consecutive patients with dementia issue that have undergone an rCBF SPECT examination. An administered activity of 1000 MBq 99mTc labelled HMPAO was injected to all patients in the study. From one single examination, five studies corresponding to different activity levels (500, 625, 750, 875 and 1000 MBq) were generated by using a gated acquisition. Iterative image reconstruction, OS-EM, including corrections for attenuation, scatter and distance dependent resolution was used. Three experienced observers, i.e. specialists in nuclear medicine, evaluated the images by rating their confidence about the fulfilment of specific image quality criteria. Seven criteria were defined in this study, developed in collaboration with experienced specialists in nuclear medicine with comprehensive knowledge on how to evaluate rCBF SPECT images. The result of the observers assessment were analysed using Visual Grading Regression, a method based on ordinal logistic regression with the aim to analyse data from visual grading experiments. The result shows that there is a significant difference in perceived image quality between 500 MBq and the reference activity, 1000 MBq, in five of the seven image quality criteria. No statistical significant degradation was found between any other activity level than 500 MBq and the reference activity (1000 MBq). This study doesn’t prove that any other activity level provides the same image quality as 1000 MBq, only because no difference was seen, but it gives an indication that the activity level could be reduced without losing too much diagnostic information. The analysis method used, Visual Grading Regression, has proven to be convenient and easy to use for this kind of optimisation studies in nuclear medicine. The defined criteria cover the areas of the brain that are of interest in blood flow examinations and the results of this study showed that the observers used the whole confidence rating scale for each criterion, which is desirable. Some of the criteria had a very low proportion of rating scores corresponding to a fulfilment of the criterion, meaning that the satisfaction of the observers is low. A reversion or adjustment of these criteria might be needed to investigate whether the low satisfaction level is due to the formulation of the criteria or if only so the particular area is difficult to assess.Möjligheten att visualisera olika sjukdomstillstånd med hjälp av bilder har inom sjukvården blivit mer och mer populärt. Nuklearmedicinska bilder framställs genom att en liten mängd av ett radioaktivt ämne injiceras i patienten och sedan detekteras med hjälp av en gammakamera. Genom att utnyttja olika upptagsmekanismer kan funktionen av ett område eller ett specifikt organ i kroppen undersökas. Blodflödet i hjärnan kan studeras genom att injicera ett radioaktivt ämne som är kopplat till en fettmolekyl, vilken passerar blod-hjärnbarriären och ackumuleras i hjärnan. Upptaget av det radioaktiva ämnet avspeglar det regionala blodflödet i hjärnan vid tidpunkten för injektionen eller strax därefter. Regionala blodflödesstudier i hjärnan utförs på patienter som stöd vid diagnostisering av demenssjukdomar då flertalet av dessa leder till en minskning av det regionala blodflödet i hjärnan. Aktivitetsmängden som injiceras påverkar både bildkvaliteten och stråldosen till patienten. För att säkerställa den aktivitet som krävs för att ge tillräckligt god bildkvalitet till lägsta möjliga stråldos krävs ett optimeringsarbete. Detta görs vanligtvis med hjälp av fysikaliska parametrar såsom brus, upplösning och kontrast. Ett annat sätt att bedöma bildkvalitet är med hjälp av erfarna observatörer som gör en visuell bedömning utifrån kliniskt relevanta bildkriterier. I arbetet introduceras en ny utvärderingsmetod, Visual Grading Regression (VGR), som inte tidigare har använts vid optimeringsstudier inom nuklearmedicin. Syftet med arbetet är att optimera aktivitetsnivån för regionala blodfödesundersökningar med gammakamera med avseende på bildkvalitet och stråldos till patient. I studien ingick 21 konsekutivt utvalda patienter med demensfrågeställning som alla genomgått en blodflödesundersökning av hjärnan med gammakameratomografi. En aktivitetsmängd på 1000 MBq injicerades till samtliga patienter. Genom att dela upp insamlingstiden i delmängder är det möjligt att generera flera bilder, vilka motsvarar olika mängder administrerad aktivitet, från en och samma undersökning. Från en studie genererades fem bilder, vilka motsvarade aktivitetsnivåer av 500, 625, 750, 875 och 1000 MBq. Kliniskt relevanta bildkriterier definierades i samarbete med en erfaren radiolog. Bilderna, motsvarande de olika aktivitetsnivåerna, bedömdes med en fyrgradig skala utifrån uppfyllandet av de definierade kriterierna. Tre erfarna radiologer med specialistkompetens inom nuklearmedicin deltog som observatörer i studien och granskade bilderna en och en i en slumpmässigt vald ordning. Resultatet av bedömningen analyserades med hjälp av den valda utvärderingsmetoden, VGR, vilken är speciellt utformad för visuella granskningsstudier och har fördelen att kunna ta hänsyn till variationer mellan patienter och mellan observatörer. Resultatet visar att en skillnad i bildkvalitet kan ses mellan bilder som motsvarar en injicerad aktivitet på 500 MBq och 1000 MBq i fem av de sju kriterierna. Ingen skillnad kan ses mellan någon av de andra aktivitetsnivåerna och referensaktiviteten, en administrerad aktivitet på 1000 MBq. Studien visar inte att någon av de andra aktivitetsnivåerna ger samma bildkvalitet som 1000 MBq, endast på grund av att ingen skillnad sågs, men det ger en indikation på att aktivitetsnivån kan sänkas utan att förlora alltför mycket diagnostisk information

Myocardial Tissue Characterization Using Magnetic Resonance Imaging

In cardiovascular disease, which is the most common cause of death in the world, early diagnosis is crucial for disease outcome. Diagnosis of cardiovascular disease can be challenging, though. Quantification of myocardial T1 and T2 relaxation times with MRI has demonstrated to be a promising method for characterizing myocardial tissue, but long measurement times have hampered clinical use. The overall aim of this doctoral thesis was to develop, validate and, in patient studies, evaluate a very fast three-dimensional method for simultaneous quantification of myocardial T1 and T2 relaxation times with whole coverage of the left ventricle. The 3D-QALAS method is presented in Paper I of this thesis. It is a method that simultaneous measures both T1 and T2 relaxation times in a three-dimensional volume of the heart. The method requires 15 heartbeats, to produce 13 short-axis slices of the left ventricle with voxelwise information of both T1 and T2 relaxation times. The 3D-QALAS method was validated in phantoms and in 10 healthy volunteers by comparing the method with reference methods and demonstrated good accuracy and robustness both in-vitro and in-vivo. In Paper II, the 3D-QALAS method was carefully validated in-vivo by investigating accuracy and precision in 10 healthy volunteers, while the clinical feasibility of the method was investigated in 23 patients with various cardiac pathologies. Repeated independent and dependent scans together with the intra-scan repeatability, demonstrated all a very good precision for the 3D-QALAS method in healthy volunteers. In Paper III and IV, the 3D-QALAS method was applied and evaluated in patient cohorts where the heart muscle alters over time. In Paper III, patients with severe aortic stenosis underwent MRI examinations with 3D-QALAS before, 3 months after and 12 months after aortic valve surgery. Changes in T1 and T2 were observed, which might be used as markers of myocardial changes with respect to edema and fibrosis, which may develop due to increased workload over a long period of time. In study IV, 3D-QALAS was used to investigate 10 breast cancer patients treated with radiation therapy prior to treatment, 2-3 weeks into treatment, and one and 6 months after completion of treatment, to investigate any changes in T1 and T2 and further if they can be correlated to unwanted irradiation of the heart during radiation therapy.

Clinical feasibility of 3D-QALAS - Single breath-hold 3D myocardial T1 and T2-mapping

Purpose: To investigate the in-vivo precision and clinical feasibility of 3D-QALAS- a novel method for simultaneous three-dimensional myocardial T1- and T2-mapping. Methods: Ten healthy subjects and 23 patients with different cardiac pathologies underwent cardiovascular 3 T MRI examinations including 3D-QALAS, MOLLI and T2-GraSE acquisitions. Precision was investigated in the healthy subjects between independent scans, between dependent scans and as standard deviation of consecutive scans. Clinical feasibility of 3D-QALAS was investigated for native and contrast enhanced myocardium in patients. Data were analyzed using mean value and 95% confidence interval, Pearson correlation, Paired t-tests, intraclass correlation and Bland-Altman analysis. Results: Average myocardial relaxation time values and SD from eight repeated acquisitions within the group of healthy subjects were 1178 +/- 18.5 ms (1.6%) for T1 with 3D-QALAS, 52.7 +/- 1.2 ms (23%) for T2 with 3D-QALAS, 1145 +/- 10.0 ms (0.9%) for Tl with MOLLI and 49.2 +/- 0.8 ms (1.6%) for T2 with GraSE. Myocardial Tl and T2 relaxation times obtained with 3D-QALAS correlated very well with reference methods; MOW for T1 (r = 0.994) and T2-GraSE for T2 (r = 0.818) in the 23 patients. Average native/post-contrast myocardial Tl values from the patients were 1166.2 ms/411.8 ms for 3D-QALAS and 1174.4 ms/438.9 ms for MOW. Average native myocardial T2 values from the patients were 53.2 ms for 3D-QAIAS and 54.4 ms for T2-GraSE. Conclusions: Repeated independent and dependent scans together with the intra-scan repeatability, demonstrated all a very good precision for the 3D-QALAS method in healthy volunteers. This study shows that 3D T1 and T2 mapping in the left ventricle is feasible in one breath hold for patients with different cardiac pathologies using 3D-QALAS. (C) 2016 Elsevier Inc. All rights reserved.Funding Agencies|Swedish Heart-Lung Foundation [20120449, 20140398]; Swedish Research Council [2014-6191]</p

Left ventricular volumes and ejection fraction from cardiac ECG-gated 15O-water positron emission tomography compared to cardiac magnetic resonance imaging using simultaneous hybrid PET/MR

Background 15O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner. Methods Twenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland–Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities. Results The correlation between PET and CMR was strong for volumes (r &gt; 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR. Conclusion LV volumes and EF can be calculated by first-pass analysis of a 15O-water PET scan with high accuracy and comparable precision as with CMR

T1 and T2 mapping for early detection of treatment-related myocardial changes in breast cancer patients

Funding agencies: This study was partially financed through ALF Grants, Region Ostergotland LIO-284291, LIO-284411, and LIO-448281, and LIU Cancer Projects Grants 2012.</p