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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.

The aim of this prospective single-institution clinical trial (NCT02002455) was to evaluate the potential of advanced post-processing methods for 18F-Fluciclovine PET and multisequence multiparametric MRI in the prediction of prostate cancer (PCa) aggressiveness, defined by Gleason Grade Group (GGG). 21 patients with PCa underwent PET/CT, PET/MRI and MRI before prostatectomy. DWI was post-processed using kurtosis (ADCk, K), mono- (ADCm), and biexponential functions (f, Dp, Df) while Logan plots were used to calculate volume of distribution (VT). In total, 16 unique PET (VT, SUV) and MRI derived quantitative parameters were evaluated. Univariate and multivariate analysis were carried out to estimate the potential of the quantitative parameters and their combinations to predict GGG 1 vs >1, using logistic regression with a nested leave-pair out cross validation (LPOCV) scheme and recursive feature elimination technique applied for feature selection. The second order rotating frame imaging (RAFF), monoexponential and kurtosis derived parameters had LPOCV AUC in the range of 0.72 to 0.92 while the corresponding value for VT was 0.85. The best performance for GGG prediction was achieved by K parameter of kurtosis function followed by quantitative parameters based on DWI, RAFF and 18F-FACBC PET. No major improvement was achieved using parameter combinations with or without feature selection. Addition of 18F-FACBC PET derived parameters (VT, SUV) to DWI and RAFF derived parameters did not improve LPOCV AUC.

We present a novel method for estimating respiratory motion using inertial measurement units (IMUs) based on microelectromechanical systems (MEMS) technology. As an application of the method we consider the amplitude gating of positron emission tomography (PET) imaging, and compare the method against a clinically used respiration motion estimation technique. The presented method can be used to detect respiratory cycles and estimate their lengths with state-of-the-art accuracy when compared to other IMU-based methods, and is the first based on commercial MEMS devices, which can estimate quantitatively both the magnitude and the phase of respiratory motion from the abdomen and chest regions. For the considered test group consisting of eight subjects with acute myocardial infarction, our method achieved the absolute breathing rate error per minute of 0.44 ± 0.23 1/min, and the absolute amplitude error of 0.24 ± 0.09 cm, when compared to the clinically used respiratory motion estimation technique. The presented method could be used to simplify the logistics related to respiratory motion estimation in PET imaging studies, and also to enable multi-position motion measurements for advanced organ motion estimation.

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.

Publisher Copyright: © 2021 The Authors We studied the association between episodic memory and cortical fibrillar β-amyloid pathology within twin pairs. Using telephone-administered cognitive screening of 1415 twin pairs in a population-based older Finnish Twin Cohort study, we identified 45 (mean [SD] age 72.9 [4.0] years, 40% women) cognitively discordant same-sex twin pairs (24 dizygotic and 21 monozygotic) without neurological or psychiatric disorders other than AD or mild cognitive impairment. In-person neuropsychological testing was conducted. Cortical amyloid was measured with carbon 11-labelled Pittsburgh compound B ([11C]PiB) positron emission tomography imaging and quantified as the average standardized uptake value ratio in cortical regions affected in AD. Larger within-twin pair differences in verbal immediate (r = -0.42) and delayed free recall (r = -0.41), and visual delayed free recall (r = -0.46) were associated with larger within-twin pair differences in [11C]PiB uptake (p's < 0.01). Correlations were not significantly different in dizygotic and monozygotic pairs suggesting that the episodic memory-cortical amyloid relationship is not confounded by genetic effects. However, larger samples are needed to draw more definitive conclusions.

Background We investigated the image quality of 11C, 68Ga, 18F and 89Zr, which have different positron fractions, physical half-lifes and positron ranges. Three small animal positron emission tomography/computed tomography (PET/CT) systems were used in the evaluation, including the Siemens Inveon, RAYCAN X5 and Molecubes β-cube. The evaluation was performed on a single scanner level using the national electrical manufacturers association (NEMA) image quality phantom and analysis protocol. Acquisitions were performed with the standard NEMA protocol for 18F and using a radionuclide-specific acquisition time for 11C, 68Ga and 89Zr. Images were assessed using percent recovery coefficient (%RC), percentage standard deviation (%STD), image uniformity (%SD), spill-over ratio (SOR) and evaluation of image quantification. Results 68Ga had the lowest %RC (18F had the highest maximum %RC (> 85%) and lowest %STD for the 5 mm rod across all systems. For 11C and 89Zr, the maximum %RC was close (> 76%) to the %RC with 18F. A larger SOR were measured in water with 11C and 68Ga compared to 18F on all systems. SOR in air reflected image reconstruction and data correction performance. Large variation in image quantification was observed, with maximal errors of 22.73% (89Zr, Inveon), 17.54% (89Zr, RAYCAN) and − 14.87% (68Ga, Molecubes). Conclusions The systems performed most optimal in terms of NEMA image quality parameters when using 18F, where 11C and 89Zr performed slightly worse than 18F. The performance was least optimal when using 68Ga, due to large positron range. The large quantification differences prompt optimization not only by terms of image quality but also quantification. Further investigation should be performed to find an appropriate calibration and harmonization protocol and the evaluation should be conducted on a multi-scanner and multi-center level.

Magnetic resonance imaging-only radiotherapy treatment planning (MRI-only RTP) and positron emission tomography (PET)-MRI imaging require generation of synthetic computed tomography (sCT) images from MRI images. In this study, initial dosimetric evaluation was performed for a previously developed MRI-based attenuation correction (MRAC) method for use in MRI-only RTP of the brain. MRAC-based sCT images were retrospectively generated from Dixon MR images of 20 patients who had previously received external beam radiation therapy (EBRT). Bone segmentation performance and Dice similarity coefficient of the sCT conversion method were evaluated for bone volumes on CT images. Dose calculation accuracy was assessed by recalculating the CT-based EBRT plans using the sCT images as the base attenuation data. Dose comparison was done for the sCT- and CT-based EBRT plans in planning target volume (PTV) and organs at risk (OAR). Parametric dose comparison showed mean relative differences of

BACKGROUND AND PURPOSE: The relationship between brain β-amyloid and regional atrophy is still incompletely understood in elderly individuals at risk of dementia. Here, we studied the associations between brain β-amyloid load and regional GM and WM volumes in older adults who were clinically evaluated as being at increased risk of cognitive decline based on cardiovascular risk factors. MATERIALS AND METHODS: Forty subjects (63–81 years of age) were recruited as part of a larger study, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability. Neuroimaging consisted of PET using (11)C Pittsburgh compound-B and T1-weighted 3D MR imaging for the measurement of brain β-amyloid and GM and WM volumes, respectively. All subjects underwent clinical, genetic, and neuropsychological evaluations for the assessment of cognitive function and the identification of cardiovascular risk factors. RESULTS: Sixteen subjects were visually evaluated as showing cortical β-amyloid (positive for β-amyloid). In the voxel-by-voxel analyses, no significant differences were found in GM and WM volumes between the samples positive and negative for β-amyloid. However, in the sample positive for β-amyloid, increases in (11)C Pittsburgh compound-B uptake were associated with reductions in GM volume in the left prefrontal (P = .02) and right temporal lobes (P = .04). CONCLUSIONS: Our results show a significant association between increases in brain β-amyloid and reductions in regional GM volume in individuals at increased risk of cognitive decline. This evidence is consistent with a model in which increases in β-amyloid incite neurodegeneration in memory systems before cognitive impairment manifests.

ObjectiveTo investigate brain amyloid pathology in a dementia-risk population defined as cardiovascular risk factors, aging, and dementia risk (CAIDE) score of at least 6 but with normal cognition and to examine associations between brain amyloid load and cognitive performance and vascular risk factors.MethodsA subgroup of 48 individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in brain 11C-Pittsburgh compound B (PiB)-PET imaging, brain MRI, and neuropsychological assessment at the beginning of the study. Lifestyle/vascular risk factors were determined as body mass index, blood pressure, total and low-density lipoprotein cholesterol, and glucose homeostasis model assessment. White matter lesions were visually rated from MRIs by a semiquantitative Fazekas score.ResultsTwenty participants (42%) had a positive PiB-PET on visual analysis. The PiB-positive group performed worse in executive functioning tests, included more participants with APOE ε4 allele (50%), and showed slightly better glucose homeostasis compared to PiB-negative participants. PiB-positive and -negative participants did not differ significantly in other cognitive domain scores or other vascular risk factors. There was no significant difference in Fazekas score between the PiB groups.ConclusionsThe high percentage of PiB-positive participants provides evidence of a successful recruitment process of the at-risk population in the main FINGER intervention trial. The results suggest a possible association between early brain amyloid accumulation and decline in executive functions. APOE ε4 was clearly associated with amyloid positivity, but no other risk factor was found to be associated with positive PiB-PET.

The purpose of this study was to evaluate 18F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa). Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq 18F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUVmax) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (VT). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455. In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p 3 + 4 tumors were significantly (p

Background Radiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [68Ga]NODAGA-RGD detects increased αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ3 integrin is expressed in viable ischemic or injured myocardium. Methods We studied 8 Finnish landrace pigs 13 ± 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery. Antithrombotic therapy was used to prevent stent occlusion. Myocardial uptake of [68Ga]NODAGA-RGD (290 ± 31 MBq) was evaluated by a 62 min dynamic PET scan. The ischemic area was defined as the regional perfusion abnormality during adenosine-induced stress by [15O]water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology. Results Stent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [68Ga]NODAGA-RGD PET showed increased tracer uptake in the ischemic area (ischemic-to-remote ratio 1.3 ± 0.20, p = 0.0034). Tissue samples from the injured areas, but not from the viable ischemic areas, showed higher [68Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [68Ga]NODAGA-RGD correlated with immunohistochemical detection of αvβ3 integrin that was expressed in the injured myocardial areas. Conclusions Cardiac [68Ga]NODAGA-RGD PET demonstrates increased myocardial αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [68Ga]NODAGA-RGD uptake indicates that it reflects αvβ3 integrin expression associated with repair of recent myocardial injury., published version, peerReviewed

In PET, corrections for photon scatter and attenuation are essential for visual and quantitative consistency. MR attenuation correction (MRAC) is generally conducted by image segmentation and assignment of discrete attenuation coefficients, which offer limited accuracy compared with CT attenuation correction. Potential inaccuracies in MRAC may affect scatter correction, because the attenuation image (μ-map) is used in single scatter simulation (SSS) to calculate the scatter estimate. We assessed the impact of MRAC to scatter correction using 2 scatter-correction techniques and 3 μ-maps for MRAC. Methods: The tail-fitted SSS (TF-SSS) and a Monte Carlo-based single scatter simulation (MC-SSS) algorithm implementations on the Philips Ingenuity TF PET/MR were used with 1 CT-based and 2 MR-based μ-maps. Data from 7 subjects were used in the clinical evaluation, and a phantom study using an anatomic brain phantom was conducted. Scatter-correction sinograms were evaluated for each scatter correction method and μ-map. Absolute image quantification was investigated with the phantom data. Quantitative assessment of PET images was performed by volume-of-interest and ratio image analysis. Results: MRAC did not result in large differences in scatter algorithm performance, especially with TF-SSS. Scatter sinograms and scatter fractions did not reveal large differences regardless of the μ-map used. TF-SSS showed slightly higher absolute quantification. The differences in volume-of-interest analysis between TF-SSS and MC-SSS were 3% at maximum in the phantom and 4% in the patient study. Both algorithms showed excellent correlation with each other with no visual differences between PET images. MC-SSS showed a slight dependency on the μ-map used, with a difference of 2% on average and 4% at maximum when a μ-map without bone was used. Conclusion: The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight 18F-FDG PET/MR brain imaging. The SSS algorithm was not affected significantly by MRAC. The performance of the MC-SSS algorithm is comparable but not superior to TF-SSS, warranting further investigations of algorithm optimization and performance with different radiotracers and time-of-flight imaging.

Background Folate receptor-β (FR-β) is a cell surface receptor that is significantly upregulated on activated macrophages during inflammation and provides a potential target for folate-based therapeutic and diagnostic agents. FR-β expression in central nervous system inflammation remains relatively unexplored. Therefore, we used focally induced acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) to study patterns of FR-β expression and evaluated its potential as an in vivo imaging target. Methods Focal EAE was induced in rats using heat-killed Bacillus Calmette-Guérin followed by activation with complete Freund’s adjuvant supplemented with Mycobacterium tuberculosis. The rats were assessed with magnetic resonance imaging and positron emission tomography/computed tomography (PET/CT) at acute (14 days) and chronic (90 days) phases of inflammation. The animals were finally sacrificed for ex vivo autoradiography of their brains. PET studies were performed using FR-β-targeting aluminum [18F]fluoride-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate ([18F]AlF-NOTA-folate, 18F-FOL) and 18 kDa translocator protein (TSPO)-targeting N-acetyl-N-(2-[11C]methoxybenzyl)-2-phenoxy-5-pyridinamine (11C-PBR28). Post-mortem immunohistochemistry was performed using anti-FR-β, anti-cluster of differentiation 68 (anti-CD68), anti-inducible nitric oxide synthase (anti-iNOS), and anti-mannose receptor C-type 1 (anti-MRC-1) antibodies. The specificity of 18F-FOL binding was verified using in vitro brain sections with folate glucosamine used as a blocking agent. Results Immunohistochemical evaluation of focal EAE lesions demonstrated anti-FR-β positive cells at the lesion border in both acute and chronic phases of inflammation. We found that anti-FR-β correlated with anti-CD68 and anti-MRC-1 immunohistochemistry; for MRC-1, the correlation was most prominent in the chronic phase of inflammation. Both 18F-FOL and 11C-PBR28 radiotracers bound to the EAE lesions. Autoradiography studies verified that this binding took place in areas of anti-FR-β positivity. A blocking assay using folate glucosamine further verified the tracer’s specificity. In the chronic phase of EAE, the lesion-to-background ratio of 18F-FOL was significantly higher than that of 11C-PBR28 (P = 0.016). Conclusion Our EAE results imply that FR-β may be a useful target for in vivo imaging of multiple sclerosis-related immunopathology. FR-β-targeted PET imaging with 18F-FOL may facilitate the monitoring of lesion development and complement the information obtained from TSPO imaging by bringing more specificity to the PET imaging armamentarium for neuroinflammation.

Dynamic Positron Emission Tomography (PET) is a valuable method in Myocardial Perfusion Imaging (MPI) allowing quantification of blood flow in the myocardial tissue. A reference test object simulating myocardial blood flow is needed. A newly developed PET phantom enables flow quantification with a known reference. However, the repetability of the flow phantom needs to be confirmed.The aim of this study was to confirm that no significant variability exists between image-derived or reference flow between subsequent measurements. Finally, we confirmed repeatability of the flow values derived by kinetic modelling from PET images of the phantom.Five repeated measurements with fixed acquisition and reconstruction protocol were performed. PET images were analysed with a software provided by the phantom vendor to derive the time-activity curves for modelling of flow values.The image-derived flow rates varied with SD of 0.89 mL/min and 0.86 mL/min between subsequent measurements. Error between image-derived and reference flow was less than 5.5 % on average within all subsequent repeats. Fluctuations between the subsequent measurements are considered to arise from the dose administration and water flow inside the phantom.In conclusion, the newly developed PET flow phantom shows high repeatability and is a reliable platform for quality control and validation studies in MPI in PET.

Background The reliable quantification of myocardial blood flow (MBF) with MRI, necessitates the correction of errors in arterial input function (AIF) caused by the T1 saturation effect. The aim of this study was to compare MBF determined by a traditional dual bolus method against a modified dual bolus approach and to evaluate both methods against PET in a porcine model of myocardial ischemia. Methods Local myocardial ischemia was induced in five pigs, which were subsequently examined with contrast enhanced MRI (gadoteric acid) and PET (O-15 water). In the determination of MBF, the initial high concentration AIF was corrected using the ratio of low and high contrast AIF areas, normalized according to the corresponding heart rates. MBF was determined from the MRI, during stress and at rest, using the dual bolus and the modified dual bolus methods in 24 segments of the myocardium (total of 240 segments, five pigs in stress and rest). Due to image artifacts and technical problems 53% of the segments had to be rejected from further analyses. These two estimates were later compared against respective rest and stress PET-based MBF measurements. Results Values of MBF were determined for 112/240 regions. Correlations for MBF between the modified dual bolus method and PET was rs = 0.84, and between the traditional dual bolus method and PET rs = 0.79. The intraclass correlation was very good (ICC = 0.85) between the modified dual bolus method and PET, but poor between the traditional dual bolus method and PET (ICC = 0.07). Conclusions The modified dual bolus method showed a better agreement with PET than the traditional dual bolus method. The modified dual bolus method was found to be more reliable than the traditional dual bolus method, especially when there was variation in the heart rate. However, the difference between the MBF values estimated with either of the two MRI-based dual-bolus methods and those estimated with the gold-standard PET method were statistically significant. Electronic supplementary material The online version of this article (10.1186/s12880-019-0359-8) contains supplementary material, which is available to authorized users.

Bariatric surgery results in notable weight loss and alleviates hyperglycemia in patients with type 2 diabetes (T2D). We aimed to characterize the vascular effects of a mixed meal and infusion of exogenous glucose-dependent insulinotropic polypeptide (GIP) in the splanchnic region in 10 obese patients with T2D before and after bariatric surgery and in 10 lean control subjects. The experiments were carried out on two separate days. Pancreatic and intestinal blood flow (BF) were measured at baseline, 20 min, and 50 min with 15O-water by using positron emission tomography and MRI. Before surgery, pancreatic and intestinal BF responses to a mixed meal did not differ between obese and lean control subjects. Compared with presurgery, the mixed meal induced a greater increase in plasma glucose, insulin, and GIP concentrations after surgery, which was accompanied by a marked augmentation of pancreatic and intestinal BF responses. GIP infusion decreased pancreatic but increased small intestinal BF similarly in all groups both before and after surgery. Taken together, these results demonstrate that bariatric surgery leads to enhanced splanchnic vascular responses as a likely consequence of rapid glucose appearance and GIP hypersecretion.

Purpose Brown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [15O]O2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE. Methods Seven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [15O]O2, [15O]H2O, and [18F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold. Results BAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2–47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus. Conclusion Our study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake. Electronic supplementary material The online version of this article (doi:10.1007/s00259-016-3364-y) contains supplementary material, which is available to authorized users.

Background Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial cell molecule and primary amine oxidase that mediates leukocyte entry to sites of inflammation. However, there is limited knowledge of the inflammation-related expression of VAP-1 in the central nervous system (CNS). Therefore, we investigated the expression of VAP-1 within the CNS vasculature in two focal rat models of experimental autoimmune encephalomyelitis (EAE) mimicking multiple sclerosis (MS). Methods EAE was induced either with Bacillus Calmette-Guérin, resulting in a delayed-type hypersensitivity-like pathogenesis (fDTH-EAE), or with myelin oligodendrocyte glycoprotein (fMOG-EAE). A subgroup of fMOG-EAE rats were treated daily with a selective VAP-1 inhibitor (LJP1586; 5 mg/kg). On 3 and 14 days after lesion activation, rat brains were assessed using magnetic resonance imaging (MRI), and ex vivo autoradiography was conducted to evaluate the binding of Gallium-68-labelled VAP-1 ligand. Histology and immunohistochemistry (OX-42, VAP-1, intercellular adhesion protein-1 [ICAM-1], P-selectin) supported the ex vivo autoradiography. Results EAE lesions showed MRI-detectable signal changes and binding of the VAP-1-targeting radiotracer in both rat models. Some of the VAP-1 positive vessels showed morphological features typical for high endothelial-like venules at sites of inflammation. Inhibition of VAP-1 activity with small molecule inhibitor, LJP1586, decreased lymphocyte density in the acute inflammatory phase of fMOG-EAE lesions (day 3, P = 0.026 vs. untreated), but not in the remission phase (day 14, P = 0.70 vs. untreated), and had no effect on the amount of OX-42-positive cells in either phase. LJP1586 treatment reduced VAP-1 and ICAM-1 expression in the acute inflammatory phase, whereas P-selectin remained not detectable at all studied stages of the disease. Conclusions Our results revealed that VAP-1 is expressed and functionally active in vasculature within the induced focal EAE lesions during the acute phase of inflammation and remains expressed after the acute inflammation has subsided. The study indicates that VAP-1 is actively involved in the development of inflammatory CNS lesions. During this process, the endothelial cell lesion-related vasculature seem to undergo a structural transformation from regular flat-walled endothelium to HEV-like endothelium.

Positron emission tomography (PET) is a non-invasive imaging technique which may be considered as the state of art for the examination of cardiac inflammation due to atherosclerosis. A fundamental limitation of PET is that cardiac and respiratory motions reduce the quality of the achieved images. Current approaches for motion compensation involve gating the PET data based on the timing of quiescent periods of cardiac and respiratory cycles. In this study, we present a novel gating method called microelectromechanical (MEMS) dual gating which relies on joint non-electrical sensors, i.e. tri-axial accelerometer and gyroscope. This approach can be used for optimized selection of quiescent phases of cardiac and respiratory cycles. Cardiomechanical activity according to echocardiography observations was investigated to confirm whether this dual sensor solution can provide accurate trigger timings for cardiac gating. Additionally, longitudinal chest motions originating from breathing were measured by accelerometric- and gyroscopic-derived respiratory (ADR and GDR) tracking. The ADR and GDR signals were evaluated against Varian real-time position management (RPM) signals in terms of amplitude and phase. Accordingly, high linear correlation and agreement were achieved between the reference electrocardiography, RPM, and measured MEMS signals. We also performed a Ge-68 phantom study to evaluate possible metal artifacts caused by the integrated read-out electronics including mechanical sensors and semiconductors. The reconstructed phantom images did not reveal any image artifacts. Thus, it was concluded that MEMS-driven dual gating can be used in PET studies without an effect on the quantitative or visual accuracy of the PET images. Finally, the applicability of MEMS dual gating for cardiac PET imaging was investigated with two atherosclerosis patients. Dual gated PET images were successfully reconstructed using only MEMS signals and both qualitative and quantitative assessments revealed encouraging results that warrant further investigation of this method.

Dual cardiac and respiratory gating is a well-known technique for motion compensation in nuclear medicine imaging. In this study, we present a new data fusion framework for dual cardiac and respiratory gating based on multidimensional microelectromechanical (MEMS) motion sensors. Our approach aims at robust estimation of the chest vibrations, that is, high-frequency precordial vibrations and low-frequency respiratory movements for prospective gating in positron emission tomography (PET), computed tomography (CT), and radiotherapy. Our sensing modality in the context of this paper is a single dual sensor unit, including accelerometer and gyroscope sensors to measure chest movements in three different orientations. Since accelerometer- and gyroscope-derived respiration signals represent the inclination of the chest, they are similar in morphology and have the same units. Therefore, we use principal component analysis (PCA) to combine them into a single signal. In contrast to this, the accelerometer- and gyroscope-derived cardiac signals correspond to the translational and rotational motions of the chest, and have different waveform characteristics and units. To combine these signals, we use independent component analysis (ICA) in order to obtain the underlying cardiac motion. From this cardiac motion signal, we obtain the systolic and diastolic phases of cardiac cycles by using an adaptive multi-scale peak detector and a short-time autocorrelation function. Three groups of subjects, including healthy controls (n = 7), healthy volunteers (n = 12), and patients with a history of coronary artery disease (n = 19) were studied to establish a quantitative framework for assessing the performance of the presented work in prospective imaging applications. The results of this investigation showed a fairly strong positive correlation (average r = 0.73 to 0.87) between the MEMS-derived (including corresponding PCA fusion) respiration curves and the reference optical camera and respiration belt sensors. Additionally, the mean time offset of MEMS-driven triggers from camera-driven triggers was 0.23 to 0.3 &plusmn, 0.15 to 0.17 s. For each cardiac cycle, the feature of the MEMS signals indicating a systolic time interval was identified, and its relation to the total cardiac cycle length was also reported. The findings of this study suggest that the combination of chest angular velocity and accelerations using ICA and PCA can help to develop a robust dual cardiac and respiratory gating solution using only MEMS sensors. Therefore, the methods presented in this paper should help improve predictions of the cardiac and respiratory quiescent phases, particularly with the clinical patients. This study lays the groundwork for future research into clinical PET/CT imaging based on dual inertial sensors.

Cardiac, respiratory, and patient body motion artifacts degrade the image quality and quantitative accuracy of the nuclear medicine imaging which may lead to incorrect diagnosis, unnecessary treatment and insufficient therapy. We present a new miniaturized system including joint micro electromechanical (MEMS) accelerometer and gyroscope sensors for simultaneous extraction of cardiac and respiratory signals. We employ two tri-axial joint MEMS sensors for selecting an optimal trigger point in a cardiac and respiratory cycle. The 6-axis motion sensing helps to detect candidate features for cardiac and respiratory gating in Positron emission tomography (PET) imaging. The aim of this study was to validate MEMS-derived signals against traditional Real-time Position Management (RPM) and electrocardiography (ECG) measurement systems in 4 healthy volunteers. High agreement and correlation were found between cardiac and respiratory cycle intervals. These promising first results warrant for further investigations.

Respiratory and cardiac motions may cause quantitative inaccuracies and hinder visual interpretation in positron emission tomography (PET) imaging. In practice, concurrent respiratory and cardiac gating is required to reliably image and identify small structures such as vulnerable coronary plaques. This study proposes a new microelectromechanical sensor (MEMS)-based gating method for eliminating motion-related artefacts. We used joint miniaturized tri-axial accelerometer and gyroscope sensors attached to the patients' chests to extract seismocardiographic (SCG) and gyrocardiographic (GCG) signals. Dual gating in cardiac patients was performed using 18F-fluorodeoxyglucose (FDG) as a tracer. The MEMS dual gating was configured and studied parallel to clinically approved methods for cardiac and respiratory gating: electrocardiography (ECG) and Real-time Position Management (RPM) systems, in PET acquisition of two atherosclerosis patients. Moreover, the radiopacity of the sensor readout-electronics was tested using a Ge-68 phantom before the clinical examinations. Accordingly, no metal artifacts were detected either in CT or PET images due to the motion sensor board, as investigated by two independent operators. Therefore, the MEMS gating board does not contain materials that could affect the visual or quantitative accuracy of PET images or CT-based attenuation correction (CTAC). Dual gated PET images were successfully reconstructed by using only cardiac and respiratory signals derived by MEMS sensors. The MEMS-gated images from the patient study were quantitatively compared to non-gated and gated images that were obtained with the reference methods. In conclusion, these results from the small patient group first imply that implementation of the MEMS gating approach is applicable in dual gated PET imaging and secondly show both qualitative and quantitative improvements in the obtained images. Thus, the first clinical experiences using MEMS cardiac-respiratory dual gating were promising and warrant for further investigations in PET imaging studies.

Bone attenuation remains a methodological challenge in hybrid PET/MR, as bone is hard to visualize via magnetic resonance imaging (MRI). Therefore, novel methods for taking into account bone attenuation in MR-based attenuation correction (MRAC) are needed. In this study, we propose a tissue-probability based attenuation correction (TPB-AC), which employs the commonly available neurological toolbox SPM8, to derive a subject-specific $\mu$ -map by segmentation of T1-weighted MR images. The procedures to derive a $\mu$ -map representing soft tissue, air and bone from the New Segment function in SPM8 and MATLAB are described. Visual and quantitative comparisons against CT-based attenuation correction (CTAC) data were performed using two $\mu$ -values ( $0.135~\hbox{cm}^{ - 1}$ and $0.145~\hbox{cm}^{ - 1}$ ) for bone. Results show improvement of visual quality and quantitative accuracy of positron emission tomography (PET) images when TPB-AC $\mu$ -map is used in PET/MR image reconstruction. Underestimation in PET images was decreased by an average of $5 \pm 2$ percent in the whole brain across all patients. In addition, the method performed well when compared to CTAC, with maximum differences (mean $ \pm$ standard deviation) of $ - 3 \pm 2$ percent and $2 \pm 4$ percent in two regions out of 28. Finally, the method is simple and computationally efficient, offering a promising platform for further development. Therefore, a subject-specific MR-based $\mu$ -map can be derived only from the tissue probability maps from the New Segment function of SPM8.