Daily standing time, dietary fiber, and intake of unsaturated fatty acids are beneficially associated with hepatic insulin sensitivity in adults with metabolic syndrome.

Background: Obesity is associated with impaired glucose metabolism and hepatic insulin resistance. The aim was to investigate the associations of hepatic glucose uptake (HGU) and endogenous glucose production (EGP) to sedentary behavior (SB), physical activity (PA), cardiorespiratory fitness, dietary factors, and metabolic risk markers. Methods: Forty-four adults with metabolic syndrome (mean age 58 [SD 7] years, BMI ranging from 25-40kg/; 25 females) were included. HGU was measured by positron emission tomography during the hyperinsulinemic-euglycemic clamp. EGP was calculated by subtracting the glucose infusion rate during clamp from the glucose rate of disappearance. SB and PA were measured with hip-worn accelerometers (26 [SD3] days). Fitness was assessed by maximal bicycle ergometry with respiratory gas measurements and dietary intake of nutrients by 4-day food diaries. Results: HGU was not associated with fitness or any of the SB or PA measures. When adjusted for sex, age, and body fat-%, HGU was associated with whole-body insulin sensitivity (ß=0.58), water-insoluble dietary fiber (ß=0.29), energy percent (E%) of carbohydrates (ß=-0.32), saccharose (ß=-0.32), mono- and polyunsaturated fatty acids (ß=0.35, ß=0.41, respectively). EGP was associated with whole-body insulin sensitivity (ß=-0.53), and low-density lipoprotein cholesterol [ß=-0.31], and when further adjusted for accelerometry wear time, EGP was associated with standing [ß=-0.43]. (p-value for all< 0.05). Conclusions: Standing more, consuming a diet rich in fiber and unsaturated fatty acids, and a lower intake of carbohydrates, especially sugar, associate beneficially with hepatic insulin sensitivity. Habitual SB, PA, or fitness may not be the primary modulators of HGU and EGP. However, these associations need to be confirmed with intervention studies.

Major brain injuries at term continue to influence DTI parameters in adolescents born very preterm: a 13-year follow-up study.

BACKGROUND: Major brain injuries in structural brain magnetic resonance imaging (MRI) at term affect concurrent diffusion tensor imaging (DTI) parameters in very preterm infants. White matter is known to gradually maturate along with increasing gestational age, which is characterized by increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD). PURPOSE: To study the difference between DTI parameters at term and 13 years in adolescents born very preterm with and without major pathologies in structural brain MRI at term. MATERIAL AND METHODS: Adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) in 2004-2006 at Turku University Hospital, Finland were included. We evaluated FA and MD at term and 13 years in 18 regions of interest using the JHU-neonate-SS atlas to compare the differences in these parameters between adolescents with and without major injuries identified on MRI at term. RESULTS: A total of 24 adolescents underwent brain MRI including DTI both at term and 13 years. Adolescents with major brain injury pathologies (n = 6) in structural MRI at term had decreased FA in the left corpus callosum and right cingulate gyrus part, and increased MD in the left corpus callosum, right anterior limb of internal capsule, and right posterior limb of the internal capsule at 13 years, in comparison with adolescents without major brain injuries (n = 18) in structural MRI at term. CONCLUSION: Our findings suggest that major brain injuries identified on structural MRI at term affect brain maturation, with adverse effects in FA and MD still during adolescence.

Cognitively healthy APOE4/4 carriers show white matter impairment associated with serum NfL and amyloid-PET.

Except for aging, carrying the APOE ε4 allele (APOE4) is the most important risk factor for sporadic Alzheimer's disease. APOE4 carriers may have reduced capacity to recycle lipids, resulting in white matter microstructural abnormalities. In this study, we evaluated whether white matter impairment measured by diffusion tensor imaging (DTI) differs between healthy individuals with a different number of APOE4 alleles, and whether white matter impairment associates with brain beta-amyloid (Aß) load and serum levels of neurofilament light chain (NfL). We studied 96 participants (APOE3/3, N = 37; APOE3/4, N = 39; APOE4/4, N = 20; mean age 70.7 (SD 5.22) years, 63% females) with a brain MRI including a DTI sequence (N = 96), Aß-PET (N = 89) and a venous blood sample for the serum NfL concentration measurement (N = 88). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) in six a priori-selected white matter regions-of-interest (ROIs) were compared between the groups using ANCOVA, with sex and age as covariates. A voxel-weighted average of FA, MD, RD and AxD was calculated for each subject, and correlations with Aß-PET and NfL levels were evaluated. APOE4/4 carriers exhibited a higher MD and a higher RD in the body of corpus callosum than APOE3/4 (p = 0.0053 and p = 0.0049, respectively) and APOE3/3 (p = 0.026 and p = 0.042). APOE4/4 carriers had a higher AxD than APOE3/4 (p = 0.012) and APOE3/3 (p = 0.040) in the right cingulum adjacent to cingulate cortex. In the total sample, composite MD, RD and AxD positively correlated with the cortical Aß load (r = 0.26 to 0.33, p < 0.013 for all) and with serum NfL concentrations (r = 0.31 to 0.36, p < 0.0028 for all). In conclusion, increased local diffusivity was detected in cognitively unimpaired APOE4/4 homozygotes compared to APOE3/4 and APOE3/3 carriers, and increased diffusivity correlated with biomarkers of Alzheimer's disease and neurodegeneration. White matter impairment seems to be an early phenomenon in the Alzheimer's disease pathologic process in APOE4/4 homozygotes.

Quantitative Perfusion Imaging with Total-Body PET.

Recently, PET systems with a long axial field of view have become the current state of the art. Total-body PET scanners enable unique possibilities for scientific research and clinical diagnostics, but this new technology also raises numerous challenges. A key advantage of total-body imaging is that having all the organs in the field of view allows studying biologic interaction of all organs simultaneously. One of the new, promising imaging techniques is total-body quantitative perfusion imaging. Currently, 15O-labeled water provides a feasible option for quantitation of tissue perfusion at the total-body level. This review summarizes the status of the methodology and the analysis and provides examples of preliminary findings on applications of quantitative parametric perfusion images for research and clinical work. We also describe the opportunities and challenges arising from moving from single-organ studies to modeling of a multisystem approach with total-body PET, and we discuss future directions for total-body imaging.

Microstructural alterations in association tracts and language abilities in schoolchildren born very preterm and with poor fetal growth.

BACKGROUND: Prematurity and perinatal risk factors may influence white matter microstructure. In turn, these maturational changes may influence language development in this high-risk population of children. OBJECTIVE: To evaluate differences in the microstructure of association tracts between preterm and term children and between preterm children with appropriate growth and those with fetal growth restriction and to study whether the diffusion tensor metrics of these tracts correlate with language abilities in schoolchildren with no severe neurological impairment. MATERIALS AND METHODS: This study prospectively followed 56 very preterm children (mean gestational age: 28.7 weeks) and 21 age- and gender-matched term children who underwent diffusion tensor imaging at a mean age of 9 years. We used automated probabilistic tractography and measured fractional anisotropy in seven bilateral association tracts known to belong to the white matter language network. Both groups participated in language assessment using five standardised tests at the same age. RESULTS: Preterm children had lower fractional anisotropy in the right superior longitudinal fasciculus 1 compared to term children (P < 0.05). Preterm children with fetal growth restriction had lower fractional anisotropy in the left inferior longitudinal fasciculus compared to preterm children with appropriate fetal growth (P < 0.05). Fractional anisotropy in three dorsal tracts and in two dorsal and one ventral tract had a positive correlation with language assessments among preterm children and preterm children with fetal growth restriction, respectively (P < 0.05). CONCLUSION: There were some microstructural differences in language-related tracts between preterm and term children and between preterm children with appropriate and those with restricted fetal growth. Children with better language abilities had a higher fractional anisotropy in distinct white matter tracts.

Relationship between liver fat content and lifestyle factors in adults with metabolic syndrome.

The aim of this study was to investigate the associations between liver fat content (LFC), sedentary behaviour (SB), physical activity (PA), fitness, diet, body composition, and cardiometabolic risk factors in adults with metabolic syndrome. A total of 44 sedentary adults (mean age 58 [SD 7] years; 25 women) with overweight or obesity participated. LFC was assessed with magnetic resonance spectroscopy and imaging, SB and PA with hip-worn accelerometers (26 [SD 3] days), fitness by maximal bicycle ergometry, body composition by air displacement plethysmography and nutrient intake by 4-day food diaries. LFC was not independently associated with SB, PA or fitness. Adjusted for sex and age, LFC was associated with body fat%, body mass index, waist circumference, triglycerides, alanine aminotransferase, and with insulin resistance markers. There was and inverse association between LFC and daily protein intake, which persisted after further adjusment with body fat%. LFC is positively associated with body adiposity and cardiometabolic risk factors, and inversely with daily protein intake. SB, habitual PA or fitness are not independent modulators of LFC. However, as PA is an essential component of healthy lifestyle, it may contribute to liver health indirectly through its effects on body composition in adults with metabolic syndrome.

Diagnostic Accuracy of 18F-FDG-PET/CT and 18F-FDG-PET/MRI in Detecting Locoregional Recurrence of HNSCC 12 Weeks after the End of Chemoradiotherapy: Single-Center Experience with PET/MRI.

Purpose: In head and neck squamous cell carcinoma (HNSCC), the early diagnosis and efficient detection of recurrences and/or residual tumor after treatment play a very important role in patient's prognosis. Positron emission tomography (PET) using 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) has become an established method for the diagnosis of suspected recurrence in head and neck carcinomas. In particular, integrated PET/MRI imaging that provides optimal soft tissue contrast and less dental implant artifacts compared to PET/CT is an intriguing technique for the follow-up imaging of HNSCC patients. The aim of this study was to evaluate the benefit of PET/MRI compared to PET/CT in post-treatment follow-up imaging of HNSCC patients. Methods: This retrospective observational cohort study consists of 104 patients from our center with histologically confirmed HNSCC. All patients received chemoradiotherapy (CRT) and underwent 18F-FDG-PET/CT (n = 52) or 18F-FDG-PET/MRI (n = 52) scan 12 weeks after the end of treatment. Image analysis was performed by two independent readers according to a five-point Likert scale analysis. Results: PET/MRI was more sensitive (1.00 vs. 0.77) than PET/CT in the detection of locoregional recurrence. PET/MRI also had better negative (1.00 vs. 0.87) predictive values. AUCs for PET/MRI and PET/CT on patient-based analysis were 0.997 (95% CI 0.989-1.000) and 0.890 (95% CI 0.806-0.974), respectively. The comparison of sensitivity, AUCs, and negative predictive values revealed a statistically significant difference, p < 0.05. In PET/CT, false-negative and positive findings were observed in the more advanced disease stages, where PET/MRI performed better. Also, false-negative findings were located in the oropharyngeal, laryngeal, and nasopharyngeal regions, where PET/MRI made no false-negative interpretations. Conclusion: Based on these results, PET/MRI might be considered the modality of choice in detecting locoregional recurrence in HNSCC patients, especially in the more advanced stages in the oral cavity, larynx, or nasopharynx.

Bioactive glass granules versus standard autologous and allogeneic bone grafts: a randomized trial of 49 adult bone tumor patients with a 10-year follow-up.

BACKGROUND AND PURPOSE: As a synthetic bone void filler, bioactive glasses (BGs) may enhance angiogenesis and osteogenesis. In this randomized trial, we compared the clinical efficacy of BG granules and standard bone grafts in patients undergoing surgery for benign bone tumors. PATIENTS AND METHODS: 49 recruited patients were randomized to receive BG granules or undergo conventional bone grafting to fill defects following tumor removal. As the standard of care, small-sized defects were filled with autologous graft, and large-sized defects were filled with allogeneic graft. The primary endpoint was treatment success at 1 year, defined by no reoperation, no tumor recurrence, and no device-related adverse events. Secondary endpoints included patient-reported outcomes (Rand-36 and pain scores) and quantitative assessment of blood flow and metabolic activity by means of 18F-fluoride PET/CT imaging. As an off-trial group, 15 children and adolescents (age < 18 years) underwent tumor removal and BG-filling, without randomization. RESULTS: At 1-year, 21 of 25 BG-treated patients (risk estimate 0.84, 95% confidence interval [CI] 0.70-0.98) and 20 of 24 patients in the standard of care group (0.83, CI 0.68-0.98) met the criteria for treatment success. The groups had similar Rand-36 scores. In patients with small defects, BG filling was associated with shorter operative time and less postoperative pain at 1 month. In patients with large defects, blood flow was similar, but BG-filled defects showed higher metabolic activity than allograft-filled defects at 1-year. The survey of the postoperative period ≥10 years revealed no BG-related adverse events. INTERPRETATION: BG granules had similar overall rates of treatment success compared with autografts and allografts, but large-scale trials are needed for the confirmation of clinical equivalence. The extended metabolic activity confirms the expected cellular responses of osseointegrated BG granules.

ASIC-E4: Interplay of Beta-Amyloid, Synaptic Density and Neuroinflammation in Cognitively Normal Volunteers With Three Levels of Genetic Risk for Late-Onset Alzheimer's Disease - Study Protocol and Baseline Characteristics.

BACKGROUND: Detailed characterization of early pathophysiological changes in preclinical Alzheimer's disease (AD) is necessary to enable development of correctly targeted and timed disease-modifying treatments. ASIC-E4 study ("Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOE ε4 carriers") combines state-of-the-art neuroimaging and fluid-based biomarker measurements to study the early interplay of three key pathological features of AD, i.e., beta-amyloid (Aß) deposition, neuroinflammation and synaptic dysfunction and loss in cognitively normal volunteers with three different levels of genetic (APOE-related) risk for late-onset AD. OBJECTIVE: Here, our objective is to describe the study design, used protocols and baseline demographics of the ASIC-E4 study. METHODS/DESIGN: ASIC-E4 is a prospective observational multimodal imaging study performed in Turku PET Centre in collaboration with University of Gothenburg. Cognitively normal 60-75-year-old-individuals with known APOE ε4/ε4 genotype were recruited via local Auria Biobank (Turku, Finland). Recruitment of the project has been completed in July 2020 and 63 individuals were enrolled to three study groups (Group 1: APOE ε4/ε4, N = 19; Group 2: APOE ε4/ε3, N = 22; Group 3: APOE ε3/ε3, N = 22). At baseline, all participants will undergo positron emission tomography imaging with tracers targeted against Aß deposition (11C-PIB), activated glia (11C-PK11195) and synaptic vesicle glycoprotein 2A (11C-UCB-J), two brain magnetic resonance imaging scans, and extensive cognitive testing. In addition, blood samples are collected for various laboratory measurements and blood biomarker analysis and cerebrospinal fluid samples are collected from a subset of participants based on additional voluntary informed consent. To evaluate the predictive value of the early neuroimaging findings, neuropsychological evaluation and blood biomarker measurements will be repeated after a 4-year follow-up period. DISCUSSION: Results of the ASIC-E4 project will bridge the gap related to limited knowledge of the synaptic and inflammatory changes and their association with each other and Aß in "at-risk" individuals. Thorough in vivo characterization of the biomarker profiles in this population will produce valuable information for diagnostic purposes and future drug development, where the field has already started to look beyond Aß.

Assessment of a digital and an analog PET/CT system for accurate myocardial perfusion imaging with a flow phantom.

In Myocardial Perfusion Imaging (MPI) with Positron Emission Tomography/Computed Tomography (PET/CT) systems, accurate quantification is essential. We assessed flow quantification accuracy over various injected activities using a flow phantom. METHODS: The study was performed on the digital 4-ring Discovery MI (DMI-20) and analog Discovery 690 (D690) PET/CT systems, using 325-1257 MBq of [15O]H2O. PET performance and flow quantification accuracy were assessed in terms of count-rates, dead-time factors (DTF), scatter fractions (SF), time-activity curves (TACs), areas-under-the-curves (AUCs) and flow values. RESULTS: On DMI-20, prompts of 12.8 Mcps, DTF of 2.06 and SF of 46.1% were measured with 1257 MBq of activity. On the D690, prompts of 6.85 Mcps, DTF of 1.57 and SF of 32.5% were measured with 1230 MBq of activity. AUC values were linear over all activities. Mean wash-in flow error was - 9% for both systems whereas wash-out flow error was - 5% and - 6% for DMI-20 and D690. With the highest activity, wash-out flow error was - 12% and - 7% for the DMI-20 and D690. CONCLUSION: DMI-20 and D690 preserved accurate flow quantification over all injected activities, with maximum error of - 12%. In the future, flow quantification accuracy over the activities and count-rates evaluated in this study should be assessed.

Maternal smoking during pregnancy negatively affects brain volumes proportional to intracranial volume in adolescents born very preterm.

Background: Maternal smoking during pregnancy has been shown to associate with smaller frontal lobe and cerebellar volumes in brain magnetic resonance imaging (MRI) at term age in very preterm infants. The aim of this study was to examine the effect of maternal smoking during pregnancy on volumetric brain MRI findings at 13 years. We hypothesized that adverse effects of smoking during pregnancy on brain volumes are still seen during adolescence. Methods: Included adolescents were born very preterm (gestational age < 32 weeks and/or birth weight ≤ 1,500 g) between April 2004 and December 2006 at the Turku University Hospital, Finland. Information on maternal smoking status (yes or no) during pregnancy was collected from medical records and maternal questionnaires before discharge. Adolescents underwent volumetric brain MRI at 13 years of age. Image post-processing was performed with FreeSurfer. Regional volumes, cortical thickness, surface area, and curvature were computed from 33 cortical regions of interest (ROIs). Additionally, volumes were calculated for 18 subcortical regions, as well as for white matter, gray matter, and intracranial volume. We normalized quantified absolute volumes for head size by dividing volumes with corresponding intracranial volumes. false discovery rate (FDR) correction for multiple comparisons across regions was used. Results: A total of 9/44 (21%) adolescents had been exposed to maternal smoking during pregnancy. No statistically significant differences in absolute volumes were observed between the groups (p > 0.05). Regarding volumes proportional to intracranial volume, the adolescents in the exposed group exhibited smaller gray matter volumes in the inferotemporal (FDR corrected p = 0.022) and parahippocampal (p = 0.018) regions compared to the unexposed group. The surface area in the exposed group was also smaller in the parahippocampal (p = 0.046) and postcentral (p = 0.046) regions compared to the unexposed group. No statistically significant differences after correction for multiple comparisons were found for either curvature or cortical thickness between the groups. Conclusion: Maternal smoking exposure during pregnancy may have long-term effects on brain volumes up to 13 years in adolescents born very preterm. Our findings emphasize the importance of smoking-free pregnancy.

Performance in Hand Coordination Tasks and Concurrent Functional MRI Findings in 13-Year-Olds Born Very Preterm.

BACKGROUND: Fine motor and coordination problems are frequently reported among adolescents born preterm. We aimed to assess performance in hand coordination tasks and to compare concurrent brain activation between adolescents born very preterm and at term at 13 years. METHODS: A total of 34 right-handed adolescents born very preterm (gestational age less than 32 weeks/birth weight ≤1500 grams) and 37 controls born at term during 2003 to 2006 in Turku University Hospital, Finland, were recruited. At 13 years, finger opposition and diadochokinesis were assessed, and brain functional magnetic resonance imaging data were acquired while the adolescents performed unimanual hand coordination tasks in response to visual cue. RESULTS: Adolescents born very preterm performed similar to controls in hand coordination tasks. The very preterm group evoked greater brain activation than the controls in the right precentral gyrus and in the right postcentral gyrus during left-hand finger opposition and in the right postcentral gyrus during left-hand diadochokinesis. Within the very preterm group, lower gestational age was associated with reduced activation in the left superior parietal lobule during right-hand diadochokinesis. Regarding left-hand tasks, lower gestational age was associated with stronger activation in the right cerebellar lobule V and left cerebellar lobule VI during finger opposition and stronger activation in the right superior parietal lobule during diadochokinesis. CONCLUSIONS: Very preterm birth affected hand coordination-related brain activation. Most of the effects were found for nondominant hand. Clinical performance during the hand coordination tasks was similar in adolescents born very preterm and controls.

The impact of susceptibility correction on diffusion metrics in adolescents.

BACKGROUND: Diffusion tensor imaging is a widely used imaging method of brain white matter, but it is prone to imaging artifacts. The data corrections can affect the measured values. OBJECTIVE: To explore the impact of susceptibility correction on diffusion metrics. MATERIALS AND METHODS: A cohort of 27 healthy adolescents (18 boys, 9 girls, mean age 12.7 years) underwent 3-T MRI, and we collected two diffusion data sets (anterior-posterior). The data were processed both with and without susceptibility artifact correction. We derived fractional anisotropy, mean diffusivity and histogram data of fiber length distribution from both the corrected and uncorrected data, which were collected from the corpus callosum, corticospinal tract and cingulum bilaterally. RESULTS: Fractional anisotropy and mean diffusivity values significantly differed when comparing the pathways in all measured tracts. The fractional anisotropy values were lower and the mean diffusivity values higher in the susceptibility-corrected data than in the uncorrected data. We found a significant difference in total tract length in the corpus callosum and the corticospinal tract. CONCLUSION: This study indicates that susceptibility correction has a significant effect on measured fractional anisotropy, and on mean diffusivity values and tract lengths. To receive reliable and comparable results, the correction should be used systematically.

Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS). Exercise training intervention in monozygotic twins discordant for body weight.

BACKGROUND: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk. METHODS: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983-1987, 1975-1979, and 1945-1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength. DISCUSSION: This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03730610 . Prospectively registered 5 November 2018.

Fingolimod treatment reverses signs of diffuse white matter damage in multiple sclerosis: A pilot study.

BACKGROUND: In multiple sclerosis (MS) diffuse normal appearing white matter (NAWM) damage may drive chronic worsening independent of relapse activity. Diffusion tensor imaging (DTI) is a nonconventional MRI technique that can be used to assess microstructural alterations in myelin and axons. The aim of our study was to investigate the effect of six months fingolimod treatment on the integrity of entire and segmented NAWM in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Ten RRMS patients initiating fingolimod treatment were included in the study. Patients underwent 3 T MRI including diffusion tensor sequences at baseline before the initiation of treatment and at six months. The mean values for fractional anisotropy (FA), and mean, radial and axial diffusivities (MD, RD and AD) were calculated within the whole NAWM and in six segmented sub-regions of NAWM (frontal, parietal, temporal, occipital, cingulate and deep NAWM). Clinical characteristics, Expanded Disability Status Scale (EDSS) and volumetric MRI data were also evaluated. RESULTS: In the cingulate NAWM FA was increased and RD was decreased significantly at six months compared to baseline (0.462 vs. 0.472, P = 0.027 and 0.000646 vs. 0.000634, P = 0.041, respectively), indicating improvements in myelin and axonal integrity following fingolimod treatment, whereas there were no alterations in cingulate MD or AD. Cingulate and temporal FA and RD correlated with T2 lesion volume percentage of cingulate and temporal areas. EDSS change correlated with change of the whole NAWM AD. CONCLUSIONS: Increased FA and decreased RD in the cingulate NAWM might suggest microstructural fingolimod-induced improvements in the normal appearing cingulate white matter. Our results support the concept that DTI can be used as a marker of diffuse neuronal damage also in interventional settings.

Assessment of myocardial viability with [15O]water PET: A validation study in experimental myocardial infarction.

BACKGROUND: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI). METHODS AND RESULTS: Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively. CONCLUSIONS: Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability.

The value of combined positron emission tomography/magnetic resonance imaging to diagnose inflammatory bowel disease: a prospective study.

BACKGROUND: The clinical utility of positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison to standard work-up with patients with known or suspected inflammatory bowel disease (IBD) is unknown. PURPOSE: To evaluate the value of 18F-fluorodeoxyglucose (18F-FDG) PET/MRI in the diagnostics of IBD and further compare the data obtained using PET/MRI to histological findings. MATERIALS AND METHODS: Ten patients with relapse in IBD or with symptoms of suspected IBD were recruited either from a gastroenterology outpatient clinic or from a hospital ward. Intestinal inflammation was assessed with histology and 18F-FDG PET/MRI. Maximum standard uptake values (SUVmax) were calculated in six regions of the intestine (small bowel, ascending, transverse, descending and sigmoid colon, and rectum) and compared to histological analysis of inflammation activity. RESULTS: The study showed that both the inflammation activity (P = 0.008) and the region of the biopsy in the intestine (P = 0.015) had a significant effect on SUV. SUVs obtained from severe inflammation activity emerged significantly from the background (P = 0.006). In addition, the SUVs obtained from moderate inflammation raised from background, but the difference was not statistically significant (P = 0.083), while SUVs of mild inflammation were at the same level with SUVs of normal bowel wall (P = 0.988). CONCLUSION: 18F-FDG PET/MRI is a promising method of detecting especially severe inflammatory bowel lesions. More data are required to define its sensitivity and specificity.

Functional Magnetic Resonance Imaging during Visual Perception Tasks in Adolescents Born Prematurely.

OBJECTIVES: Impairments in visual perception are among the most common developmental difficulties related to being born prematurely, and they are often accompanied by problems in other developmental domains. Neural activation in participants born prematurely and full-term during tasks that assess several areas of visual perception has not been studied. To better understand the neural substrates of the visual perceptual impairments, we compared behavioral performance and brain activations during visual perception tasks in adolescents born very preterm (birth weight ≤1500 g or gestational age <32 weeks) and full-term. METHODS: Tasks assessing visual closure, discrimination of a deviating figure, and discrimination of figure and ground from the Motor-Free Visual Perception Test, Third Edition were performed by participants born very preterm (n = 37) and full-term (n = 34) at 12 years of age during functional magnetic resonance imaging. RESULTS: Behavioral performance in the visual perception tasks did not differ between the groups. However, during the visual closure task, brain activation was significantly stronger in the group born very preterm in a number of areas including the frontal, anterior cingulate, temporal, and posterior medial parietal/cingulate cortices, as well as in parts of the cerebellum, thalamus, and caudate nucleus. CONCLUSIONS: Differing activations during the visual closure task potentially reflect a compensatory neural process related to premature birth or lesser neural efficiency or may be a result of the use of compensatory behavioral strategies in the study group born very preterm.

Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9 years of age.

BACKGROUND: Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. OBJECTIVE: The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. MATERIALS AND METHODS: The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. RESULTS: Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (P<0.05, corrected for multiple comparison) in dorsolateral prefrontal caudate and ventrolateral prefrontal caudate tracts as compared to term-born children. We found negative correlations between the diffusion tensor imaging metrics of frontostriatal tracts and inhibition functions (P<0.05, corrected for multiple comparison) in very preterm children. CONCLUSION: Prematurity has a long-term effect on frontostriatal white matter microstructure that might contribute to difficulties in executive functioning.

Quantification of Myocardial Blood Flow by Machine Learning Analysis of Modified Dual Bolus MRI Examination.

Contrast-enhanced magnetic resonance imaging (MRI) is a promising method for estimating myocardial blood flow (MBF). However, it is often affected by noise from imaging artefacts, such as dark rim artefact obscuring relevant features. Machine learning enables extracting important features from such noisy data and is increasingly applied in areas where traditional approaches are limited. In this study, we investigate the capacity of machine learning, particularly support vector machines (SVM) and random forests (RF), for estimating MBF from tissue impulse response signal in an animal model. Domestic pigs (n = 5) were subjected to contrast enhanced first pass MRI (MRI-FP) and the impulse response at different regions of the myocardium (n = 24/pig) were evaluated at rest (n = 120) and stress (n = 96). Reference MBF was then measured using positron emission tomography (PET). Since the impulse response may include artefacts, classification models based on SVM and RF were developed to discriminate noisy signal. In addition, regression models based on SVM, RF and linear regression (for comparison) were developed for estimating MBF from the impulse response at rest and stress. The classification and regression models were trained on data from 4 pigs (n = 168) and tested on 1 pig (n = 48). Models based on SVM and RF outperformed linear regression, with higher correlation (R SVM 2 = 0.81, R RF 2 = 0.74, R linear_regression 2 = 0.60; ρSVM = 0.76, ρRF = 0.76, ρlinear_regression = 0.71) and lower error (RMSESVM = 0.67 mL/g/min, RMSERF = 0.77 mL/g/min, RMSElinear_regression = 0.96 mL/g/min) for predicting MBF from MRI impulse response signal. Classifier based on SVM was optimal for detecting impulse response signals with artefacts (accuracy = 92%). Modified dual bolus MRI signal, combined with machine learning, has potential for accurately estimating MBF at rest and stress states, even from signals with dark rim artefacts. This could provide a protocol for reliable and easy estimation of MBF, although further research is needed to clinically validate the approach.