Publications by authors named "Jarmo Teuho"

34 Publications

A Respiratory Motion Estimation Method Based on Inertial Measurement Units for Gated Positron Emission Tomography.

Sensors (Basel) 2021 Jun 9;21(12). Epub 2021 Jun 9.

Turku PET Centre, University of Turku and Turku University Hospital, 20521 Turku, Finland.

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.
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http://dx.doi.org/10.3390/s21123983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228885PMC
June 2021

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

J Nucl Cardiol 2021 May 4. Epub 2021 May 4.

Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, 20521, Finland.

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 [O]HO. 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.
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http://dx.doi.org/10.1007/s12350-021-02631-9DOI Listing
May 2021

Evaluation of image quality with four positron emitters and three preclinical PET/CT systems.

EJNMMI Res 2020 Dec 10;10(1):155. Epub 2020 Dec 10.

Turku PET Centre, University of Turku, Turku, Finland.

Background: We investigated the image quality of C, Ga, F and Zr, 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 F and using a radionuclide-specific acquisition time for C, Ga and Zr. 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: Ga had the lowest %RC (< 62%) across all systems. F had the highest maximum %RC (> 85%) and lowest %STD for the 5 mm rod across all systems. For C and Zr, the maximum %RC was close (> 76%) to the %RC with F. A larger SOR were measured in water with C and Ga compared to F 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% (Zr, Inveon), 17.54% (Zr, RAYCAN) and - 14.87% (Ga, Molecubes).

Conclusions: The systems performed most optimal in terms of NEMA image quality parameters when using F, where C and Zr performed slightly worse than F. The performance was least optimal when using Ga, 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.
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http://dx.doi.org/10.1186/s13550-020-00724-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728905PMC
December 2020

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery.

Nutr Metab Cardiovasc Dis 2020 11 15;30(12):2363-2371. Epub 2020 Jul 15.

Turku PET Centre, University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland. Electronic address:

Background And Aims: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients.

Methods And Results: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002).

Conclusion: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity.

Clinical Trial Registration Number: NCT01373892.
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http://dx.doi.org/10.1016/j.numecd.2020.07.010DOI Listing
November 2020

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

Ann Biomed Eng 2021 Feb 20;49(2):653-662. Epub 2020 Aug 20.

Diagnostic Imaging Center, Kuopio University Hospital, PO Box 100, 70029 KYS, Kuopio, Finland.

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  = 0.81, R  = 0.74, R  = 0.60; ρ = 0.76, ρ = 0.76, ρ = 0.71) and lower error (RMSE = 0.67 mL/g/min, RMSE = 0.77 mL/g/min, RMSE = 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.
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http://dx.doi.org/10.1007/s10439-020-02591-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851105PMC
February 2021

Prediction of prostate cancer aggressiveness using F-Fluciclovine (FACBC) PET and multisequence multiparametric MRI.

Sci Rep 2020 06 10;10(1):9407. Epub 2020 Jun 10.

Department of Diagnostic Radiology, University of Turku, Turku, Finland.

The aim of this prospective single-institution clinical trial (NCT02002455) was to evaluate the potential of advanced post-processing methods for F-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 (ADC, K), mono- (ADC), and biexponential functions (f, D, D) while Logan plots were used to calculate volume of distribution (V). In total, 16 unique PET (V, 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 V was 0.85. he best performance for GGG prediction was achieved by K parameter of kurtosis function followed by quantitative parameters based on DWI, RAFF and F-FACBC PET. No major improvement was achieved using parameter combinations with or without feature selection. Addition of F-FACBC PET derived parameters (V, SUV) to DWI and RAFF derived parameters did not improve LPOCV AUC.
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http://dx.doi.org/10.1038/s41598-020-66255-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287051PMC
June 2020

Assessment of MRI-Based Attenuation Correction for MRI-Only Radiotherapy Treatment Planning of the Brain.

Diagnostics (Basel) 2020 May 14;10(5). Epub 2020 May 14.

Department of Physics and Astronomy, University of Turku, Vesilinnantie 5, FI-20014 Turku, Finland.

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 <0.4% for PTV and <1.0% for OARs. Mean gamma index pass rates of 95.7% with the 2%/2 mm agreement criterion and 96.5% with the 1%/1 mm agreement criterion were determined for glioma and metastasis patients, respectively. Based on the results, MRI-only RTP using sCT images generated from MRAC images can be a feasible alternative for radiotherapy of the brain.
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http://dx.doi.org/10.3390/diagnostics10050299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278007PMC
May 2020

Myocardial perfusion reserve of kidney transplant patients is well preserved.

EJNMMI Res 2020 Feb 10;10(1). Epub 2020 Feb 10.

Department of Medicine, Division of Nephrology, Turku University Hospital, PL 52, Kiinamyllynkatu 4-8, 20521, Turku, Finland.

Background: Chronic kidney disease (CKD) is associated with endothelial dysfunction and increased cardiovascular mortality. Endothelial dysfunction can be studied measuring myocardial perfusion reserve (MPR). MPR is the ratio of stress and rest myocardial perfusion (MP) and reflects the capacity of vascular bed to increase perfusion and microvascular responsiveness. In this pilot study, our aim was to assess MPR of 19 patients with kidney transplant (CKD stages 2-3) and of ten healthy controls with quantitative [O]HO positron emission tomography (PET) method.

Results: Basal MP was statistically significantly higher at rest in the kidney transplant patients than in the healthy controls [1.3 (0.4) ml/min/g and 1.0 (0.2) ml/min/g, respectively, p = 0.0015]. After correction of basal MP by cardiac workload [MP = basal MP/individual rate pressure product (RPP) × average RPP of the healthy controls], the difference between the groups disappeared [0.9 (0.2)  ml/min/g and 1.0 (0.3) ml/min/g, respectively, p = 0.55)]. There was no difference in stress MP between the kidney transplant patients and the healthy subjects [3.8 (1.0) ml/min/g and 4.0 (0.9) ml/min/g, respectively, p = 0.53]. Although MPR was reduced, MPR (stress MP/basal MP) did not differ between the kidney transplant patients and the healthy controls [4.1 (1.1) and 4.3 (1.6), respectively, p = 0.8].

Conclusions: MP during stress is preserved in kidney transplant patients with CKD stage 2-3. The reduced MPR appears to be explained by increased resting MP. This is likely linked with increased cardiac workload due to sympathetic overactivation in kidney transplant patients.
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http://dx.doi.org/10.1186/s13550-020-0606-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010868PMC
February 2020

Folate receptor-targeted positron emission tomography of experimental autoimmune encephalomyelitis in rats.

J Neuroinflammation 2019 Dec 3;16(1):252. Epub 2019 Dec 3.

Turku PET Centre, University of Turku, Turku, Finland.

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 [F]fluoride-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate ([F]AlF-NOTA-folate, F-FOL) and 18 kDa translocator protein (TSPO)-targeting N-acetyl-N-(2-[C]methoxybenzyl)-2-phenoxy-5-pyridinamine (C-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 F-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 F-FOL and C-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 F-FOL was significantly higher than that of C-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 F-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.
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http://dx.doi.org/10.1186/s12974-019-1612-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892159PMC
December 2019

A Computational Framework for Data Fusion in MEMS-Based Cardiac and Respiratory Gating.

Sensors (Basel) 2019 Sep 24;19(19). Epub 2019 Sep 24.

Turku PET Centre, Turku University and Turku University Central Hospital, 20500 Turku, Finland.

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 ± 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.
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http://dx.doi.org/10.3390/s19194137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811750PMC
September 2019

Quantification of porcine myocardial perfusion with modified dual bolus MRI - a prospective study with a PET reference.

BMC Med Imaging 2019 07 26;19(1):58. Epub 2019 Jul 26.

Diagnostic Imaging Center, Kuopio University Hospital, PO Box 100, 70029, Kuopio, KYS, Finland.

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 r = 0.84, and between the traditional dual bolus method and PET r = 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.
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http://dx.doi.org/10.1186/s12880-019-0359-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660956PMC
July 2019

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

J Nucl Cardiol 2019 Jul 17. Epub 2019 Jul 17.

Turku PET Centre, University of Turku, Turku, Finland.

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 [O]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 [O]water PET perfusion imaging are useful for the assessment of myocardial viability.
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http://dx.doi.org/10.1007/s12350-019-01818-5DOI Listing
July 2019

System evaluation of automated production and inhalation of O-labeled gaseous radiopharmaceuticals for the rapid O-oxygen PET examinations.

EJNMMI Phys 2018 Dec 19;5(1):37. Epub 2018 Dec 19.

Department of Radiology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan.

Background: O-oxygen inhalation PET is unique in its ability to provide fundamental information regarding cerebral hemodynamics and energy metabolism in man. However, the use of O-oxygen has been limited in a clinical environment largely attributed to logistical complexity, in relation to a long study period, and the need to produce and inhale three sets of radiopharmaceuticals. Despite the recent works that enabled shortening of the PET examination period, radiopharmaceutical production has still been a limiting factor. This study was aimed to evaluate a recently developed radiosynthesis/inhalation system that automatically supplies a series of O-labeled gaseous radiopharmaceuticals of CO, O, and CO at short intervals.

Methods: The system consists of a radiosynthesizer which produces CO, O, and CO; an inhalation controller; and an inhalation/scavenging unit. All three parts are controlled by a common sequencer, enabling automated production and inhalation at intervals less than 4.5 min. The gas inhalation/scavenging unit controls to sequentially supply of qualified radiopharmaceuticals at given radioactivity for given periods at given intervals. The unit also scavenges effectively the non-inhaled radioactive gases. Performance and reproducibility are evaluated.

Results: Using an O-dedicated cyclotron with deuteron of 3.5 MeV at 40 μA, CO, O, and CO were sequentially produced at a constant rate of 1400, 2400, and 2000 MBq/min, respectively. Each of radiopharmaceuticals were stably inhaled at < 4.5 min intervals with negligible contamination from the previous supply. The two-hole two-layered face mask with scavenging device minimized the gaseous radioactivity surrounding subject's face, while maintaining the normocapnia during examination periods. Quantitative assessment of net administration doses could be assessed using a pair of radio-detectors at inlet and scavenging tubes, as 541 ± 149, 320 ± 103, 523 ± 137 MBq corresponding to 2-min supply of 2574 ± 255 MBq for CO, and 1-min supply of 2220 ± 766 and 1763 ± 174 for O and CO, respectively.

Conclusions: The present system allowed for automated production and inhalation of series of O-labeled radiopharmaceuticals as required in the rapid O-Oxygen PET protocol. The production and inhalation were reproducible and improved logistical complexity, and thus the use of O-oxygen might have become practically applicable in clinical environments.
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http://dx.doi.org/10.1186/s40658-018-0236-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300454PMC
December 2018

Vascular adhesion protein-1 is actively involved in the development of inflammatory lesions in rat models of multiple sclerosis.

J Neuroinflammation 2018 May 1;15(1):128. Epub 2018 May 1.

Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland.

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.
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http://dx.doi.org/10.1186/s12974-018-1152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930736PMC
May 2018

Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown Adipose Tissue.

Diabetes 2018 07 12;67(7):1226-1236. Epub 2018 Apr 12.

Turku PET Centre, University of Turku, Turku, Finland

Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors. These effects may be mediated partly via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents. To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography radioligand [F]FMPEP- and measured BAT activation in parallel with the glucose analog [F]fluorodeoxyglucose. Activation by cold exposure markedly increased CB1R density and glucose uptake in the BAT of lean men. Similarly, β3-receptor agonism increased CB1R density in the BAT of rats. In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes. Our results highlight that CB1Rs are significant for human BAT activity, and the CB1Rs provide a novel therapeutic target for BAT activation in humans.
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http://dx.doi.org/10.2337/db17-1366DOI Listing
July 2018

Brain amyloid load and its associations with cognition and vascular risk factors in FINGER Study.

Neurology 2018 01 20;90(3):e206-e213. Epub 2017 Dec 20.

From the Turku PET Centre (N.K., J. Johansson, J.T., J. Joutsa, J.R., E.R., J.P., J.O.R.), University of Turku; Division of Clinical Neurosciences (N.K., J. Joutsa, E.R., J.O.R.), Turku University Hospital; Department of Radiology (R.P.), Turku University Hospital and University of Turku, Finland; Athinoula A. Martinos Center for Biomedical Imaging (J. Joutsa), Massachusetts General Hospital and Harvard Medical School, Charlestown; Berenson-Allen Center for Noninvasive Brain Stimulation (J. Joutsa), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Public Health Solutions (T.N., T.L., M.K.), Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Division of Clinical Geriatrics (T.N., A.S., M.K.), Center for Alzheimer Research, NVS, and Aging Research Center (A.S., M.K.), Karolinska Institutet, Stockholm, Sweden; Department of Neurology (A.S., R.S., Y.L., H.S., M.K.), Institute of Clinical Medicine, and Institute of Public Health and Clinical Nutrition (T.L.), University of Eastern Finland, Kuopio; Department of Neurology (T.H., H.S.), Kuopio University Hospital; Research and Service Centre for Occupational Health (T.P.), Finnish Institute of Occupational Health, Helsinki; Joint Municipal Authority for North Karelia Social and Health Services (T.L.), Joensuu; National Institute for Health and Welfare (A.J.); and Department of Biostatistics (T.V.), University of Turku and Turku University Hospital, Turku, Finland.

Objective: To 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.

Methods: A subgroup of 48 individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in brain C-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.

Results: Twenty participants (42%) had a positive PiB-PET on visual analysis. The PiB-positive group performed worse in executive functioning tests, included more participants with 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.

Conclusions: The 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. ε4 was clearly associated with amyloid positivity, but no other risk factor was found to be associated with positive PiB-PET.
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http://dx.doi.org/10.1212/WNL.0000000000004827DOI Listing
January 2018

Prospective evaluation of F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial).

Eur J Nucl Med Mol Imaging 2018 03 16;45(3):355-364. Epub 2017 Nov 16.

Turku PET Centre, Turku, Finland.

Purpose: The purpose of this study was to evaluate F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa).

Methods: Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV) 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 (V). 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.

Results: 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 < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV and V of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes.

Conclusions: Quantitative F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.
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http://dx.doi.org/10.1007/s00259-017-3875-1DOI Listing
March 2018

A novel dual gating approach using joint inertial sensors: implications for cardiac PET imaging.

Phys Med Biol 2017 Oct 4;62(20):8080-8101. Epub 2017 Oct 4.

Turku PET Center, University of Turku, Finland. Department of Future Technologies, University of Turku, Finland.

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.
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http://dx.doi.org/10.1088/1361-6560/aa8b09DOI Listing
October 2017

Imaging of αβ integrin expression in experimental myocardial ischemia with [Ga]NODAGA-RGD positron emission tomography.

J Transl Med 2017 06 19;15(1):144. Epub 2017 Jun 19.

Turku PET Centre, University of Turku, 20521, Turku, Finland.

Background: Radiolabeled RGD peptides detect αβ integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [Ga]NODAGA-RGD detects increased αβ integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αβ 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 [Ga]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 [O]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, [Ga]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 [Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [Ga]NODAGA-RGD correlated with immunohistochemical detection of αβ integrin that was expressed in the injured myocardial areas.

Conclusions: Cardiac [Ga]NODAGA-RGD PET demonstrates increased myocardial αβ integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [Ga]NODAGA-RGD uptake indicates that it reflects αβ integrin expression associated with repair of recent myocardial injury.
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http://dx.doi.org/10.1186/s12967-017-1245-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477135PMC
June 2017

Quantitative Evaluation of 2 Scatter-Correction Techniques for F-FDG Brain PET/MRI in Regard to MR-Based Attenuation Correction.

J Nucl Med 2017 10 23;58(10):1691-1698. Epub 2017 Mar 23.

Department of Medical Physics, Turku University Hospital, Turku, Finland.

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. 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. 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. The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight F-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.
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http://dx.doi.org/10.2967/jnumed.117.190231DOI Listing
October 2017

Effects of meal and incretins in the regulation of splanchnic blood flow.

Endocr Connect 2017 Apr 3;6(3):179-187. Epub 2017 Mar 3.

Turku PET CentreUniversity of Turku, Turku, Finland

Objective: Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions.

Design: A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed.

Methods: Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with O-water and O-carbon monoxide, respectively.

Results: Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1.

Conclusion: Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.
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http://dx.doi.org/10.1530/EC-17-0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428912PMC
April 2017

Bariatric Surgery Enhances Splanchnic Vascular Responses in Patients With Type 2 Diabetes.

Diabetes 2017 04 17;66(4):880-885. Epub 2017 Jan 17.

Turku PET Centre, University of Turku, Turku, Finland

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 O-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.
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http://dx.doi.org/10.2337/db16-0762DOI Listing
April 2017

Human brown adipose tissue [(15)O]O2 PET imaging in the presence and absence of cold stimulus.

Eur J Nucl Med Mol Imaging 2016 Sep 19;43(10):1878-86. Epub 2016 Mar 19.

Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.

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 [(15)O]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 [(15)O]O2, [(15)O]H2O, and [(18)F]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.
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http://dx.doi.org/10.1007/s00259-016-3364-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969352PMC
September 2016

Modulation of the structural properties of mesoporous silica nanoparticles to enhance the T-weighted MR imaging capability.

J Mater Chem B 2016 Mar 12;4(9):1720-1732. Epub 2016 Feb 12.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

In this study, we have investigated the contrast enhancement of Gd(iii) incorporated nanoparticle-based contrast agents (CA) by the modulation of the synthesis and structural parameters of the mesoporous silica nanoparticle (MSN) matrix. In the optimisation process, the structure of the MSN matrix, post-synthesis treatment protocols, as well as the source and incorporation routes of paramagnetic gadolinium centers were considered, with the aim to shorten the T weighted relaxation time. After preliminary evaluation of the prepared MSNs as nanoparticulate T/positive contrast agents based on relaxivity, the structure of the MSN matrix was affirmed as the most decisive property to enhance the r relaxivity value, alongside the incorporation route of paramagnetic Gd(iii) centers. Based on these findings, the most promising Gd(iii) incorporated MSN-based CA candidate was further evaluated for its cytocompatibility and intensity enhancement by in vitro phantom MR-imaging of labeled cells. Furthermore, pre-labeled tumors grown on a chick embryo chorioallantoic membrane (CAM) were imaged as an in vivo model on a 3T clinical MRI scanner. Our findings show that the optimized MSN-based CA design enables proper access of water to Gd-centers in the selected MSN matrices, and simultaneously decreases the required amount of Gd(iii) content per mass when evaluated against the other MSNs. Consequently, the required Gd amount on a per-dose basis is significantly decreased with regard to clinically used Gd-based CAs for T-weighted MR imaging.
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http://dx.doi.org/10.1039/c5tb02371hDOI Listing
March 2016

Effect of Attenuation Correction on Regional Quantification Between PET/MR and PET/CT: A Multicenter Study Using a 3-Dimensional Brain Phantom.

J Nucl Med 2016 May 28;57(5):818-24. Epub 2016 Jan 28.

National Cerebral and Cardiovascular Center, Osaka, Japan.

Unlabelled: A spatial bias in brain PET/MR exists compared with PET/CT, because of MR-based attenuation correction. We performed an evaluation among 4 institutions, 3 PET/MR systems, and 4 PET/CT systems using an anthropomorphic brain phantom, hypothesizing that the spatial bias would be minimized with CT-based attenuation correction (CTAC).

Methods: The evaluation protocol was similar to the quantification of changes in neurologic PET studies. Regional analysis was conducted on 8 anatomic volumes of interest (VOIs) in gray matter on count-normalized, resolution-matched, coregistered data. On PET/MR systems, CTAC was applied as the reference method for attenuation correction.

Results: With CTAC, visual and quantitative differences between PET/MR and PET/CT systems were minimized. Intersystem variation between institutions was +3.42% to -3.29% in all VOIs for PET/CT and +2.15% to -4.50% in all VOIs for PET/MR. PET/MR systems differed by +2.34% to -2.21%, +2.04% to -2.08%, and -1.77% to -5.37% when compared with a PET/CT system at each institution, and these differences were not significant (P ≥ 0.05).

Conclusion: Visual and quantitative differences between PET/MR and PET/CT systems can be minimized by an accurate and standardized method of attenuation correction. If a method similar to CTAC can be implemented for brain PET/MRI, there is no reason why PET/MR should not perform as well as PET/CT.
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http://dx.doi.org/10.2967/jnumed.115.166165DOI Listing
May 2016

68Ga-DOTA-Siglec-9--a new imaging tool to detect synovitis.

Arthritis Res Ther 2015 Nov 3;17:308. Epub 2015 Nov 3.

Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland.

Introduction: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule, which upon inflammation is rapidly translocated from intracellular sources to the endothelial cell surface. We have recently discovered that sialic acid- binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1 and that 68Ga-labeled Siglec-9 motif peptide facilitates in vivo imaging of inflammation. This study evaluated the feasibility of 68Ga-DOTA-Siglec-9 positron emission tomography (PET) for the assessment of synovitis.

Methods: Rabbits with synovial inflammation were injected with 18F-FDG or 68Ga-DOTA-Siglec-9 and studied by gamma counting and autoradiography. Certain rabbits were also examined with magnetic resonance imaging (MRI). After PET imaging, rabbits were intravenously administered with anti-VAP-1 antibody to evaluate luminal expression of VAP-1 by immunohistochemistry. Finally, binding of Siglec-9 peptide and VAP-1 positive vessels were evaluated by double staining of rheumatoid arthritis synovium.

Results: Intra-articular injection of hemagglutinin induced mild synovial inflammation in rabbit knee with luminal expression of VAP-1. Synovitis was clearly visualized by 68Ga-DOTA-Siglec-9 PET in addition to 18F-FDG-PET and MRI. Compared with the 18F-FDG, the ex vivo inflamed-to-control synovium ratio of 68Ga-DOTA-Siglec-9 was similar (1.7 ± 0.4 vs. 1.5 ± 0.2, P = 0.32). Double staining revealed that Siglec-9 peptide binds to VAP-1 positive vessels in human rheumatoid synovium.

Conclusion: Ga-DOTA-Siglec-9 PET tracer detected VAP-1 positive vasculature in the mild synovitis of rabbits comparable with 18F-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.
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http://dx.doi.org/10.1186/s13075-015-0826-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632466PMC
November 2015

[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs.

PLoS One 2015 29;10(6):e0131332. Epub 2015 Jun 29.

Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.

Objective: Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.

Methods: First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).

Results: Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).

Conclusions: We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131332PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487365PMC
March 2016

A novel respiratory gating method for oncologic positron emission tomography based on bioimpedance approach.

Ann Nucl Med 2015 May 1;29(4):351-8. Epub 2015 Feb 1.

Diagnostic Imaging Centre, Kuopio University Hospital, Kuopio, Finland,

Objective: Respiratory motion causes loss of image quality and inaccuracy of quantification in oncologic positron emission tomography (PET) imaging. This study introduces a bioimpedance-based gating method for compensation of respiratory motion artefacts.

Methods: The bioimpedance-based respiratory gating method was studied parallel to a clinically used respiratory gating method [Real-time Position Management by Varian Medical Systems] in 4D PET/CT acquisition of 9 oncologic patients. The quantitative analysis consisted of the evaluation of tumour SUVpeak, SUVmax and volume. Additionally, target-to-background ratios as well as motion in cranial-caudal and anterior-posterior directions were measured. The evaluation was performed with amplitude- and time-based gating using averaged attenuation correction maps.

Results: Bioimpedance gating resulted in 17.7-18.9 % increase in mean SUVpeak and 20.0-21.4 % decrease in mean volume compared to non-gated images. The maximum motion measured from the bioimpedance-gated images was 19 mm in cranial-caudal direction and 9 mm in anterior-posterior direction.

Conclusions: Bioimpedance-based respiratory gating compensates the adverse effects of motion in oncologic PET imaging.
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http://dx.doi.org/10.1007/s12149-015-0953-yDOI Listing
May 2015