Publications by authors named "Tommi Noponen"

39 Publications

Prospective comparison of F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

Eur J Nucl Med Mol Imaging 2021 Mar 13. Epub 2021 Mar 13.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

Purpose: To prospectively compare F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).

Methods: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.

Results: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively.

Conclusion: F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.

Clinical Trial Registration: Clinicaltrials.gov ID: NCT03537391.
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http://dx.doi.org/10.1007/s00259-021-05296-1DOI Listing
March 2021

The feasibility of [F]EF5-PET/CT to image hypoxia in ovarian tumors: a clinical study.

EJNMMI Res 2020 Sep 10;10(1):103. Epub 2020 Sep 10.

Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.

Rationale: Evaluation of the feasibility of [F]EF5-PET/CT scan in identifying hypoxic lesions in ovarian tumors in prospective clinical setting.

Methods: Fifteen patients with a suspected malignant ovarian tumor were scanned with [F]EF5 and [F]FDG-PET/CT preoperatively. The distribution of [F]EF5-uptake, total intraabdominal metabolic tumor volume (TMTV), and hypoxic subvolume (HSV) were assessed.

Results: [F]EF5-PET/CT suggested hypoxia in 47% (7/15) patients. The median HSV was 87 cm (31% of TMTV). The [F]EF5-uptake was detected in primary tumors and in four patients also in intra-abdominal metastases. The [F]EF5-uptake in cancer tissue was low compared to physiological excretory pathways, complicating the interpretation of PET/CT images.

Conclusions: [F]EF5-PET/CT is not feasible in ovarian cancer imaging in clinical setting due to physiological intra-abdominal [F]EF5-accumulation. However, it may be useful when used complementarily to FDG-PET/CT.
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http://dx.doi.org/10.1186/s13550-020-00689-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483702PMC
September 2020

A Prospective Comparison of F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

Eur Urol Oncol 2020 Jul 13. Epub 2020 Jul 13.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

Background: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa).

Objective: To compare standard staging modalities with newer and potentially more accurate imaging modalities.

Design, Setting, And Participants: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities.

Outcome Measurements And Statistical Analysis: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, Tc-hydroxymethylene diphosphonate (Tc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and F-prostate-specific membrane antigen-1007 (F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging.

Results And Limitations: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions.

Conclusions: Despite the risk of false positive bone lesions, F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa.

Patient Summary: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.
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http://dx.doi.org/10.1016/j.euo.2020.06.012DOI Listing
July 2020

Progressive dopaminergic defect in a patient with primary progressive multiple sclerosis.

Mult Scler Relat Disord 2019 Nov 7;36:101385. Epub 2019 Sep 7.

Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Department of Medical Physics, Turku University Hospital, Turku, Finland.

Dopamine has a modulatory role in a number of autoimmune diseases, but there are no published cases of longitudinal dopaminergic imaging in multiple sclerosis (MS). Here we report a patient with primary progressive multiple sclerosis (PPMS) who was scanned twice with brain dopamine transporter single photon emission computed tomography (SPECT) with an interval of four years. The results showed a loss of tracer binding that corresponded to a 4-7 fold steeper decline than in normal ageing. The finding points to a relevant role of nigrostriatal dopaminergic degeneration in the pathological process of PPMS.
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http://dx.doi.org/10.1016/j.msard.2019.101385DOI Listing
November 2019

Burden of non-motor symptoms in unclear parkinsonism and tremor: A study with [I]FP-CIT SPECT.

J Neurol Sci 2019 Sep 19;404:124-127. Epub 2019 Jul 19.

Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland.

Background: Non-motor symptoms (NMSs) are clearly more prevalent in Parkinson's disease (PD) patients compared to healthy individuals. However, NMSs are also common in the elderly and other neurological conditions, and thus, it is not known whether NMSs could be used to differentiate PD from parkinsonism/tremor without dopamine deficiency.

Methods: We prospectively evaluated NMSs immediately before brain dopamine transporter (DAT) [I]FP-CIT SPECT scanning in 193 patients with unclear parkinsonism/tremor. According to the clinical follow-up and imaging results, 84 patients had PD. NMSs and their correlations with striatal DAT binding were investigated in PD patients and in parkinsonism/tremor patients with normal dopamine function.

Results: Total NMS burden, anxiety or depression did not differ between PD patients and patients with normal DAT binding. DAT-normal patients reported more perception-related (p = 0.045) and attention/memory-related NMSs than PD patients (p < 0.001). Total NMS score did not correlate with striatal DAT binding in either group.

Conclusions: In clinically uncertain cases, the total NMS burden cannot be used as a tool in distinguishing PD patients from patients with non-dopaminergic parkinsonism/tremor. Clinical screening of NMSs appears equally important in all patients with parkinsonism.
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http://dx.doi.org/10.1016/j.jns.2019.07.025DOI Listing
September 2019

Bupropion Causes Misdiagnosis in Brain Dopamine Transporter Imaging for Parkinsonism.

Clin Neuropharmacol 2019 Sep/Oct;42(5):181-183

Department of Neurology, University of Turku.

Objective: The objective of this study was to report long-lasting effects of bupropion on brain dopamine transporter (DAT) in a patient with depression and parkinsonism.

Methods: The patient was a 52-year old man who had been treated with 150 mg/d of bupropion for depression. The patient developed cognitive problems, bradykinesia, and reduced stride length for which he was scanned with [I]FP-CIT single photon emission computed tomography after the recommended 1-week discontinuation of bupropion. Levodopa treatment trial was initiated without a response. Eleven months later, the patient was scanned for a second time after a 1-month stoppage of bupropion.

Results: The first scan was abnormal with left putamen specific binding ratio of 1.99 (SDs from the reference value mean, -2.40), right putamen of 2.27 (SD, -1.84), left caudate of 2.33 (SD, -2.26), and right caudate of 2.29 (SD, -2.18). The second scan (after 1-month discontinuation) was normal, and specific binding ratios had increased from 5.2% to 31.7% in all striatal regions as compared with the first scan. Brain magnetic resonance imaging and [F]fluorodeoxyglucose positron emission tomography imaging were normal, and there was no levodopa response or other features supporting neurodegenerative parkinsonism.

Conclusions: Bupropion has previously generally been discontinued 1 week prior DAT imaging, which meets the recommended, albeit arbitrary, time interval of 5 plasma clearance half-lives before the scan. One-week discontinuation of bupropion before DAT imaging may be insufficiently short. Our case shows that longer medication washout and rescan may be needed when there is contradiction between the imaging result and clinical outcome in patients with medications affecting DAT binding.
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http://dx.doi.org/10.1097/WNF.0000000000000359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791561PMC
March 2020

No link between striatal dopaminergic axons and dopamine transporter imaging in Parkinson's disease.

Mov Disord 2019 10 24;34(10):1562-1566. Epub 2019 Jun 24.

Department of Neurology, University of Turku, Turku, Finland.

Background: Brain dopamine transporter binding has been considered a possible biomarker for nigrostriatal degeneration in PD.

Objective: To investigate whether dopamine transporter binding is associated with the number of dopaminergic neurites in the putamen.

Methods: Tyrosine hydroxylase-positive nerve fibers were counted from postmortem putamen sections taken from 14 parkinsonism patients who had been scanned with dopamine transporter single-photon emission computed tomography antemortem. Fiber counts were correlated with putamen dopamine transporter binding and SN neuron counts.

Results: The putamen dopamine transporter specific binding ratio did not correlate with the putamen tyrosine hydroxylase-positive axon counts (r = 0.00; P = 1.0; PD patients: r = 0.07; P = 0.86). The nigra neuron counts had a positive correlation with the putamen tyrosine hydroxylase-positive axon counts.

Conclusions: Striatal dopamine transporter imaging does not associate with axonal nor somal loss of the nigrostriatal neurons in PD. It may reflect dopaminergic activity rather than number of surviving neurons or their striatal projection axons. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27777DOI Listing
October 2019

Individual parkinsonian motor signs and striatal dopamine transporter deficiency: a study with [I-123]FP-CIT SPECT.

J Neurol 2019 Apr 28;266(4):826-834. Epub 2019 Jan 28.

Division of Clinical Neurosciences, University of Turku, Turku University Hospital, POB 52, 20521, Turku, Finland.

Introduction: Total parkinsonian motor symptom severity correlates with presynaptic striatal dopamine function in patients with Parkinson's disease. There is a lack of studies that have investigated the associations between parkinsonian motor signs and striatal dopaminergic deficiency in patients with parkinsonism of an unknown origin. Identification of specific motor signs associated with the highest likelihood of striatal dopamine deficiency could aid the differential diagnostics of parkinsonian and tremor syndromes.

Methods: In this cross-sectional clinical and imaging study, detailed motor examinations were performed for 221 patients with parkinsonism or tremor of an unknown origin immediately before dopamine transporter (DAT) [I-123]FP-CIT SPECT imaging. Region-of-interest and voxel-based methods were used to investigate striatal DAT deficiency in relation to individual motor signs.

Results: Upper extremity rigidity and facial expression were the only motor signs that differentiated patients with normal and abnormal striatal DAT function. The presence of any upper extremity rigidity showed the highest likelihood of DAT deficiency (OR 4.79, 95% CI 1.56-14.75, P = 0.006) followed by reduced facial expression (OR 2.14, 95% CI 1.14-4.00, P = 0.018). In patients with DAT deficits, reduced facial expression was associated with DAT deficiency specifically in the caudate nucleus, and increased upper extremity rigidity was associated with DAT loss in the dorsal putamen (FWE-corrected P < 0.05).

Conclusions: Increased upper extremity muscle tone and hypomimia are independently associated with a higher likelihood of striatal hypodopaminergic imaging finding. This information can be used as a factor when the clinical need of auxiliary investigations, such as DAT SPECT, is considered for patients with parkinsonism.
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http://dx.doi.org/10.1007/s00415-019-09202-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420881PMC
April 2019

Comparison of standardized uptake values between Tc-HDP SPECT/CT and F-NaF PET/CT in bone metastases of breast and prostate cancer.

EJNMMI Res 2019 Jan 24;9(1). Epub 2019 Jan 24.

Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland.

Background: Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the clinical practice. The aim of this study is to evaluate the feasibility of quantitative SPECT for measuring metastatic bone uptake in breast and prostate cancer by comparing standard uptake values (SUVs) measured with Tc-HDP SPECT/CT and F-NaF PET/CT.

Methods: Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent both Tc-HDP SPECT/CT and F-NaF PET/CT within 14 days of each other. The SPECT and PET data were reconstructed using ordered-subset expectation-maximization algorithms achieving quantitative images. Metastatic and benign skeletal lesions visible in both data sets were identified, and their maximum, peak, and mean SUVs (SUV, SUV, and SUV) were determined. SUV ratios (SUVRs) between the lesions and adjacent normal appearing bone were also calculated. Linear regression was used to evaluate the correlations between the SUVs of SPECT and PET and Bland-Altman plots to evaluate the differences between the SUVs and SUVRs of SPECT and PET.

Results: A total of 231 skeletal lesions, 129 metastatic and 102 benign, were analyzed. All three SUV measures correlated very strongly between SPECT and PET (R ≥ 0.80, p < 0.001) when all lesions were included, and the PET SUVs were significantly higher than SPECT SUVs (p < 0.001). The median differences were 21%, 12%, and 19% for SUV, SUV, and SUV, respectively. On the other hand, the SUVRs were similar between SPECT and PET with median differences of 2%, - 9%, and 2% for SUVR, SUVR, and SUVR, respectively.

Conclusion: The strong correlation between SUVs and similar SUVRs of Tc-HDP SPECT/CT and F-NaF PET/CT demonstrate that SPECT is an applicable tool for clinical quantification of bone metabolism in osseous metastases in breast and prostate cancer patients.
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http://dx.doi.org/10.1186/s13550-019-0475-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346696PMC
January 2019

A Comparative Ga-Citrate and Ga-Chloride PET/CT Imaging of Osteomyelitis in the Rat Tibia.

Contrast Media Mol Imaging 2018 25;2018:9892604. Epub 2018 Feb 25.

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

There may be some differences in the behavior of Ga-chloride and Ga-citrate leading to different accumulation profiles. This study compared Ga-citrate and Ga-chloride PET/CT imaging under standardized experimental models. Diffuse tibial osteomyelitis and uncomplicated bone healing rat models were used ( = 32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using Ga-citrate or Ga-chloride, and tissue accumulation was confirmed by analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. In PET/CT imaging, the SUV of Ga-chloride and Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp.) were significantly higher ( = 0.0019 and = 0.0020, resp.) than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.). In osteomyelitic tibias, the SUV of Ga-citrate was significantly higher than the uptake of Ga-chloride ( = 0.0017). In animals with uncomplicated bone healing, no difference in the SUV of Ga-chloride or Ga-citrate was seen in the operated tibias. This study further corroborates the use of Ga-citrate for PET imaging of osteomyelitis.
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http://dx.doi.org/10.1155/2018/9892604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845485PMC
July 2019

Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease.

Neurology 2017 Apr 10;88(15):1461-1467. Epub 2017 Mar 10.

From the Division of Clinical Neurosciences (L.S., J.J., V.K.), Turku University Hospital, Turku, Finland; Department of Neurology (L.S., J.J., V.K.) and Turku PET Centre (J.J., T.N., V.K.), University of Turku; and Departments of Pathology (K.K., M.G.) and Clinical Physiology and Nuclear Medicine (T.N.), Turku University Hospital and University of Turku, Finland.

Objective: To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD).

Methods: Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses.

Results: Mean putamen SBR did not correlate with the number of substantia nigra TH-positive ( = -0.11, = 0.66) or neuromelanin-containing ( = -0.07, = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included.

Conclusions: This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.
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http://dx.doi.org/10.1212/WNL.0000000000003810DOI Listing
April 2017

Evaluation of motion-correction methods for dual-gated cardiac positron emission tomography/computed tomography imaging.

Nucl Med Commun 2016 Sep;37(9):956-68

aTurku PET Centre, Turku University Hospital bDepartment of Mathematics and Statistics cDepartment of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku dDepartment of Nuclear Medicine eDepartment of Medical Physics, Turku University Hospital, Turku fKnowledge Intensive Services, VTT Technical Research Centre of Finland, Tampere, Finland gHammersmith Imanet Ltd hInstitute of Nuclear Medicine, University College London, London, UK.

Background: Dual gating is a method of dividing the data of a cardiac PET scan into smaller bins according to the respiratory motion and the ECG of the patient. It reduces the undesirable motion artefacts in images, but produces several images for interpretation and decreases the quality of single images. By using motion-correction techniques, the motion artefacts in the dual-gated images can be corrected and the images can be combined into a single motion-free image with good statistics.

Aim: The aim of the present study is to develop and evaluate motion-correction methods for cardiac PET studies. We have developed and compared two different methods: computed tomography (CT)/PET-based and CT-only methods.

Methods: The methods were implemented and tested with a cardiac phantom and three patient datasets. In both methods, anatomical information of CT images is used to create models for the cardiac motion.

Results: In the patient study, the CT-only method reduced motion (measured as the centre of mass of the myocardium) on average 43%, increased the contrast-to-noise ratio on average 6.0% and reduced the target size on average 10%. Slightly better figures (51, 6.9 and 28%) were obtained with the CT/PET-based method. Even better results were obtained in the phantom study for both the CT-only method (57, 68 and 43%) and the CT/PET-based method (61, 74 and 52%).

Conclusion: We conclude that using anatomical information of CT for motion correction of cardiac PET images, both respiratory and pulsatile motions can be corrected with good accuracy.
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http://dx.doi.org/10.1097/MNM.0000000000000539DOI Listing
September 2016

Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease.

J Nucl Med 2015 Jul 7;56(7):1036-41. Epub 2015 May 7.

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.

Unlabelled: Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease.

Methods: Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain.

Results: We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05.

Conclusion: Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease.
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http://dx.doi.org/10.2967/jnumed.115.153734DOI Listing
July 2015

Prospective evaluation of planar bone scintigraphy, SPECT, SPECT/CT, 18F-NaF PET/CT and whole body 1.5T MRI, including DWI, for the detection of bone metastases in high risk breast and prostate cancer patients: SKELETA clinical trial.

Acta Oncol 2016 2;55(1):59-67. Epub 2015 Apr 2.

d Turku PET Centre , Turku , Finland.

Purpose: Detection of bone metastases in breast and prostate cancer patients remains a major clinical challenge. The aim of the current trial was to compare the diagnostic accuracy of (99m)Tc-hydroxymethane diphosphonate ((99m)Tc-HDP) planar bone scintigraphy (BS), (99m)Tc-HDP SPECT, (99m)Tc-HDP SPECT/CT, (18)F-NaF PET/CT and whole body 1.5 Tesla magnetic resonance imaging (MRI), including diffusion weighted imaging, (wbMRI+DWI) for the detection of bone metastases in high risk breast and prostate cancer patients.

Material And Methods: Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent (99m)Tc-HDP BS, (99m)Tc-HDP SPECT, (99m)Tc-HDP SPECT/CT, (18)F-NaF PET/CT and wbMRI+DWI. Five independent reviewers interpreted each individual modality without the knowledge of other imaging findings. The final metastatic status was based on the consensus reading, clinical and imaging follow-up (minimal and maximal follow-up time was 6, and 32 months, respectively). The bone findings were compared on patient-, region-, and lesion-level.

Results: (99m)Tc-HDP BS was false negative in four patients. In the region-based analysis, sensitivity values for (99m)Tc-HDP BS, (99m)Tc-HDP SPECT, (99m)Tc-HDP SPECT/CT, (18)F-NaF PET/CT, and wbMRI+DWI were 62%, 74%, 85%, 93%, and 91%, respectively. The number of equivocal findings for (99m)Tc-HDP BS, (99m)Tc-HDP SPECT, (99m)Tc-HDP SPECT/CT, (18)F-NaF PET/CT and wbMRI+DWI was 50, 44, 5, 6, and 4, respectively.

Conclusion: wbMRI+DWI showed similar diagnostic accuracy to (18)F-NaF PET/CT and outperformed (99m)Tc-HDP SPECT/CT, and (99m)Tc-HDP BS.
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http://dx.doi.org/10.3109/0284186X.2015.1027411DOI Listing
December 2016

Linear relation between spirometric volume and the motion of cardiac structures: MRI and clinical PET study.

J Nucl Cardiol 2016 06 20;23(3):475-85. Epub 2015 Feb 20.

Turku PET Centre, University of Turku and Turku University Hospital, PO BOX 52, 20521, Turku, Finland.

Background: In cardiac PET, CT, and MRI respiration is major reason for impaired image quality of small targets such as coronary arteries. Strong correlations between heart motion and respiratory signals have been detected but quantitative relation between signals and motion of cardiac structures in MRI or PET is not reported .

Methods: Relation between spirometric lung volume or pressure belt signal and motion of coronary vessels in MRI was studied on nine healthy volunteers. Spirometry was further applied to (18)F-FDG cardiac PET study to determine quantitative relation between volume change and motion of center of myocardium activity (CMA) on nine CAD patients.

Results: Correlation coefficients (CC) between vessel motions and volume or pressure changes were 0.90-0.92 or 0.86-0.84, respectively. The linear equations based on volume or pressure changes derived 2.0-2.6 or 2.9-3.3 mm mean estimation error for vessel motions. In PET CC value of 0.93 was determined between volume changes and CMA motions. The linear equation based on volume change derived maximum estimation error of 2.5 mm for CMA motion.

Conclusion: The spirometric volume change linearly estimates motion of myocardium in PET with good accuracy and have potential to guide selection of optimal number of respiratory gates in cardiac PET.
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http://dx.doi.org/10.1007/s12350-014-0057-4DOI Listing
June 2016

Effects of aging and gender on striatal and extrastriatal [123I]FP-CIT binding in Parkinson's disease.

Neurobiol Aging 2015 Apr 22;36(4):1757-1763. Epub 2015 Jan 22.

Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.

To investigate the effects of aging and gender on brain dopamine and serotonin transporter bindings, we analyzed [(123)I]FP-CIT single-photon emission computed tomography scans of 231 Parkinson's disease (PD) patients and 230 controls. An automated region-of-interest-based method (BRASS automated analysis software) was used for striatal regions and a voxel-based method (Statistical Parametric Mapping software, SPM8) for the entire brain. In controls, aging was associated with a decline of 3.6%-4.6% per decade in striatal binding. Multiple extrastriatal regions also showed age-related declines. In PD patients, age-related declines were only observed in the caudate nuclei, thalamus, olfactory, and cingulate cortices with a comparable rate of decline as that in controls. Female subjects had higher caudate nucleus binding compared with males with a similar near-significant difference in the right putamen. The results demonstrate that the aging effect is limited in PD, which is possibly because of disease-related excess variation, and the results do not support the theory of accelerated aging of the dopaminergic system in PD. Women have higher caudate nucleus dopamine transporter binding compared with men in both normal and degenerated dopamine systems.
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http://dx.doi.org/10.1016/j.neurobiolaging.2015.01.016DOI Listing
April 2015

Akinetic crisis in Parkinson's disease is associated with a severe loss of striatal dopamine transporter function: a report of two cases.

Case Rep Neurol 2014 Sep 26;6(3):275-80. Epub 2014 Nov 26.

Visby Lasarett, Visby, Sweden.

Akinetic crisis or acute akinesia is a life-threatening complication of Parkinson's disease (PD) with unknown pathophysiological mechanisms. Clinically, it resembles the neuroleptic malignant syndrome, and dopaminergic drugs are transiently ineffective in the acute phase of the condition. There are no published dopaminergic functional imaging studies on PD patients with akinetic crisis. Here we report 2 advanced PD patients with akinetic crisis who were scanned with SPECT using brain dopamine transporter ligand [(123)I]FP-CIT. The first patient was additionally scanned before the condition developed, and the second patient was scanned after recovery. Striatal dopamine transporter binding was lower during than before the crisis, and both patients showed a nearly complete loss of dopamine transporter binding during the crisis. Serial imaging showed that the uptake remained negligible despite an improvement in motor function after recovery. Akinetic crisis in PD appears to be associated with a particularly severe loss of presynaptic striatal dopamine function that does not improve after recovery. Apart from presynaptic dopaminergic function, other dopaminergic or nondopaminergic mechanisms are involved in the clinical improvement of motor functions after akinetic crisis in PD.
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http://dx.doi.org/10.1159/000369448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280458PMC
September 2014

Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease.

Eur J Nucl Med Mol Imaging 2014 Oct 28;41(10):1931-7. Epub 2014 May 28.

Division of Clinical Neurosciences, University of Turku and Turku University Hospital, POB 52, 20521, Turku, Finland,

Purpose: Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor.

Methods: [(123)I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates.

Results: Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen.

Conclusion: The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor.
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http://dx.doi.org/10.1007/s00259-014-2796-5DOI Listing
October 2014

Myocardial blood flow and its transit time, oxygen utilization, and efficiency of highly endurance-trained human heart.

Basic Res Cardiol 2014 Jul 28;109(4):413. Epub 2014 May 28.

Turku PET Centre, University of Turku and Turku University Hospital, PO Box 52, 20521, Turku, Finland,

Highly endurance-trained athlete's heart represents the most extreme form of cardiac adaptation to physical stress, but its circulatory alterations remain obscure. In the present study, myocardial blood flow (MBF), blood mean transit time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and efficiency of cardiac work were quantified in highly trained male endurance athletes and control subjects at rest and during supine cycling exercise using [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF were lower in athletes both at rest and during exercise. OEF increased in response to exercise in both groups, but was higher in athletes (70 ± 21 vs. 63 ± 11 % at rest and 86 ± 13 vs. 73 ± 10 % during exercise). MTT was longer and vascular resistance higher in athletes both at rest and during exercise, but arterial content of 2,3-diphosphoglycerate (oxygen affinity) was unchanged. MVO2 per gram of myocardium trended (p = 0.08) lower in athletes both at rest and during exercise, while myocardial efficiency of work and MVO2 per beat were not different between groups. Arterial levels of free fatty acids were ~twofold higher in athletes likely leading to higher myocardial fatty acid oxidation and hence oxygen cost, which may have blunted the bradycardia-induced decrease in MVO2. Finally, the observed group differences in MBF, OEF, MTT and vascular resistance remained significant also after they were controlled for differences in MVO2. In conclusion, in highly endurance-trained human heart, increased myocardial blood transition time enables higher oxygen extraction levels with a lower myocardial blood flow and higher vascular resistance. These physiological adaptations to exercise training occur independently of the level of oxygen consumption and together with training-induced bradycardia may serve as mechanisms to increase functional reserve of the human heart.
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http://dx.doi.org/10.1007/s00395-014-0413-1DOI Listing
July 2014

Brown adipose tissue function is accompanied by cerebral activation in lean but not in obese humans.

J Cereb Blood Flow Metab 2014 Jun 26;34(6):1018-23. Epub 2014 Mar 26.

1] Turku PET Centre, University of Turku, Turku, Finland [2] Turku PET Centre, Turku University Hospital, Turku, Finland.

Brown adipose tissue (BAT) is able to generate heat and dissipate energy in response to cold exposure in mammals. It has recently been acknowledged that adult humans also have functional BAT, whose metabolic activity is reduced in obesity. In healthy humans, the cerebral mechanisms that putatively control BAT function are unclear. By using positron emission tomography (PET), we showed that cold-induced BAT activation is associated with glucose metabolism in the cerebellum, thalamus, and cingulate, temporoparietal, lateral frontal, and occipital cortices in lean participants, whereas no such associations were found under warm control conditions. The cold-induced increase in cerebral glucose metabolism was more robust in lean than obese participants. Cerebral glucose metabolism was not associated with skeletal muscle or white adipose tissue glucose uptake under warm or cold conditions. In conclusion, BAT metabolism was accompanied by the activation of specific cerebral regions, and this shows an uncharacterized role that the brain plays in the regulation of BAT function. In obese participants, the cold-induced response in cerebral activity was attenuated that provides a clue for obesity-induced impairment in BAT metabolism.
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http://dx.doi.org/10.1038/jcbfm.2014.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050247PMC
June 2014

Hyperthyroidism increases brown fat metabolism in humans.

J Clin Endocrinol Metab 2014 Jan 20;99(1):E28-35. Epub 2013 Dec 20.

Turku PET Centre (M.L., J.O., M.S., J.C.H., A.K., K.A.V., P.N.), University of Turku, 20520 Turku, Finland; Division of Endocrinology (C.S.-J.), Department of Medicine, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland; Department of Endocrinology (M.S., P.J.) and Department of Nuclear Medicine (T.N.), Turku University Hospital, 20520 Turku, Finland; Department of Investigative Radiology (H.I.), National Cerebral and Cardiovascular Center Research Institute, Osaka 565-8565, Japan; Department of Medical Physics (N.K.), Faculty of Medicine, Kagawa University, Kagawa 760-0016, Japan; and Medical Genetics (S.E.), Department of Medical Biochemistry, University of Gothenburg, 411 37 Gothenburg, Sweden.

Context: Thyroid hormones are important regulators of brown adipose tissue (BAT) development and function. In rodents, BAT metabolism is up-regulated by thyroid hormones.

Objective: The purpose of this article was to investigate the impact of hyperthyroidism on BAT metabolism in humans.

Design: This was a follow-up study using positron emission tomography imaging.

Main Outcome Measures: Glucose uptake (GU) and perfusion of BAT, white adipose tissue, skeletal muscle, and thyroid gland were measured using [18F]2-fluoro-2-deoxy-D-glucose and [15O]H2O and positron emission tomography in 10 patients with overt hyperthyroidism and in 8 healthy participants. Five of the hyperthyroid patients were restudied after restoration of euthyroidism. Supraclavicular BAT was quantified with magnetic resonance imaging or computed tomography and energy expenditure (EE) with indirect calorimetry.

Results: Compared with healthy participants, hyperthyroid participants had 3-fold higher BAT GU (2.7±2.3 vs 0.9±0.1 μmol/100 g/min, P=.0013), 90% higher skeletal muscle GU (P<.005), 45% higher EE (P<.005), and a 70% higher lipid oxidation rate (P=.001). These changes were reversible after restoration of euthyroidism. During hyperthyroidism, serum free T4 and free T3 were strongly associated with EE and lipid oxidation rates (P<.001). TSH correlated inversely with BAT and skeletal muscle glucose metabolism (P<.001). Hyperthyroidism had no effect on BAT perfusion, whereas it stimulated skeletal muscle perfusion (P=.04). Thyroid gland GU did not differ between hyperthyroid and euthyroid study subjects.

Conclusions: Hyperthyroidism increases GU in BAT independently of BAT perfusion. Hyperthyroid patients are characterized by increased skeletal muscle metabolism and lipid oxidation rates.
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http://dx.doi.org/10.1210/jc.2013-2312DOI Listing
January 2014

Preclinical evaluation of a radioiodinated fully human antibody for in vivo imaging of vascular adhesion protein-1-positive vasculature in inflammation.

J Nucl Med 2013 Aug 11;54(8):1315-9. Epub 2013 Jul 11.

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

Unlabelled: Vascular adhesion protein-1 (VAP-1) is an endothelial glycoprotein mediating leukocyte trafficking from blood to sites of inflammation. BTT-1023 is a fully human monoclonal anti-VAP-1 antibody developed to treat inflammatory diseases. In this study, we preclinically evaluated radioiodinated BTT-1023 for inflammation imaging.

Methods: Rabbits were intravenously injected with radioiodinated BTT-1023. Distribution and pharmacokinetics were assessed by PET/CT up to 72 h after injection. Human radiation dose estimates for (124)I-BTT-1023 were extrapolated. Additionally, rabbits with chemically induced synovitis were imaged with (123)I-BTT-1023 SPECT/CT.

Results: Radioiodinated BTT-1023 cleared rapidly from blood circulation and distributed to liver and thyroid. Inflamed joints were delineated by SPECT/CT. The estimated human effective dose due to (124)I-BTT-1023 was 0.55 mSv/MBq, if blockage of thyroid uptake is assumed.

Conclusion: The radioiodinated BTT-1023 was able to detect mild inflammation in vivo. Clinical (124)I-BTT-1023 PET studies with injected radioactivity of 0.5-0.7 MBq/kg may be justified.
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http://dx.doi.org/10.2967/jnumed.113.120295DOI Listing
August 2013

Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans.

Obesity (Silver Spring) 2013 Nov 13;21(11):2279-87. Epub 2013 Jun 13.

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

Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed.

Design And Methods: Using positron emission tomography (PET), cold- and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss.

Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender.

Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.
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http://dx.doi.org/10.1002/oby.20456DOI Listing
November 2013

Validation of indirect calorimetry for measurement of energy expenditure in healthy volunteers undergoing pressure controlled non-invasive ventilation support.

J Clin Monit Comput 2012 Feb 30;26(1):37-43. Epub 2011 Dec 30.

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital and University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland.

The aim of this validation study was to assess the reliability of gas exchange measurement with indirect calorimetry among subjects who undergo non-invasive ventilation (NIV). Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in twelve healthy volunteers. Respiratory quotient (RQ) and resting energy expenditure (REE) were then calculated from the measured VO2 and VCO2 values. During the measurement period the subjects were breathing spontaneously and ventilated using NIV. Two different sampling air flow values 40 and 80 l/min were used. The gas leakage from the measurement setup was assessed with a separate capnograph. The mean weight of the subjects was 93 kg. Their mean body mass index was 29 (range 22-40) kg/m2. There was no statistically significant difference in the measured values for VO2, VCO2, RQ and REE during NIV-supported breathing and spontaneous breathing. The change of sampling air flow had no statistically significant effect on any of the above parameters. We found that REE can be accurately measured with an indirect calorimeter also during NIV-supported breathing and the change of sampling air flow does not distort the gas exchange measurement. A higher sampling air flow in indirect calorimetry decreases the possibility for air leakages in the measurement system and increases the reliability of REE measurement.
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http://dx.doi.org/10.1007/s10877-011-9331-zDOI Listing
February 2012

Spontaneous hemodynamic oscillations during human sleep and sleep stage transitions characterized with near-infrared spectroscopy.

PLoS One 2011 17;6(10):e25415. Epub 2011 Oct 17.

Department of Biomedical Engineering and Computational Science, Aalto University, Aalto, Espoo, Finland.

Understanding the interaction between the nervous system and cerebral vasculature is fundamental to forming a complete picture of the neurophysiology of sleep and its role in maintaining physiological homeostasis. However, the intrinsic hemodynamics of slow-wave sleep (SWS) are still poorly known. We carried out 30 all-night sleep measurements with combined near-infrared spectroscopy (NIRS) and polysomnography to investigate spontaneous hemodynamic behavior in SWS compared to light (LS) and rapid-eye-movement sleep (REM). In particular, we concentrated on slow oscillations (3-150 mHz) in oxy- and deoxyhemoglobin concentrations, heart rate, arterial oxygen saturation, and the pulsation amplitude of the photoplethysmographic signal. We also analyzed the behavior of these variables during sleep stage transitions. The results indicate that slow spontaneous cortical and systemic hemodynamic activity is reduced in SWS compared to LS, REM, and wakefulness. This behavior may be explained by neuronal synchronization observed in electrophysiological studies of SWS and a reduction in autonomic nervous system activity. Also, sleep stage transitions are asymmetric, so that the SWS-to-LS and LS-to-REM transitions, which are associated with an increase in the complexity of cortical electrophysiological activity, are characterized by more dramatic hemodynamic changes than the opposite transitions. Thus, it appears that while the onset of SWS and termination of REM occur only as gradual processes over time, the termination of SWS and onset of REM may be triggered more abruptly by a particular physiological event or condition. The results suggest that scalp hemodynamic changes should be considered alongside cortical hemodynamic changes in NIRS sleep studies to assess the interaction between the autonomic and central nervous systems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025415PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197192PMC
April 2012

Accelerometer-based method for correcting signal baseline changes caused by motion artifacts in medical near-infrared spectroscopy.

J Biomed Opt 2011 Aug;16(8):087005

Aalto University School of Science, Department of Biomedical Engineering and Computational Science, P.O. Box 12200, FI-00076 Aalto, Finland.

In medical near-infrared spectroscopy (NIRS), movements of the subject often cause large step changes in the baselines of the measured light attenuation signals. This prevents comparison of hemoglobin concentration levels before and after movement. We present an accelerometer-based motion artifact removal (ABAMAR) algorithm for correcting such baseline motion artifacts (BMAs). ABAMAR can be easily adapted to various long-term monitoring applications of NIRS. We applied ABAMAR to NIRS data collected in 23 all-night sleep measurements and containing BMAs from involuntary movements during sleep. For reference, three NIRS researchers independently identified BMAs from the data. To determine whether the use of an accelerometer improves BMA detection accuracy, we compared ABAMAR to motion detection based on peaks in the moving standard deviation (SD) of NIRS data. The number of BMAs identified by ABAMAR was similar to the number detected by the humans, and 79% of the artifacts identified by ABAMAR were confirmed by at least two humans. While the moving SD of NIRS data could also be used for motion detection, on average 2 out of the 10 largest SD peaks in NIRS data each night occurred without the presence of movement. Thus, using an accelerometer improves BMA detection accuracy in NIRS.
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http://dx.doi.org/10.1117/1.3606576DOI Listing
August 2011

Different metabolic responses of human brown adipose tissue to activation by cold and insulin.

Cell Metab 2011 Aug;14(2):272-9

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

We investigated the metabolism of human brown adipose tissue (BAT) in healthy subjects by determining its cold-induced and insulin-stimulated glucose uptake and blood flow (perfusion) using positron emission tomography (PET) combined with computed tomography (CT). Second, we assessed gene expression in human BAT and white adipose tissue (WAT). Glucose uptake was induced 12-fold in BAT by cold, accompanied by doubling of perfusion. We found a positive association between whole-body energy expenditure and BAT perfusion. Insulin enhanced glucose uptake 5-fold in BAT independently of its perfusion, while the effect on WAT was weaker. The gene expression level of insulin-sensitive glucose transporter GLUT4 was also higher in BAT as compared to WAT. In conclusion, BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner.
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http://dx.doi.org/10.1016/j.cmet.2011.06.012DOI Listing
August 2011

Impaired cerebral vasoreactivity may cause cerebral blood volume dip following obstructive sleep apnea termination.

Sleep Breath 2012 Jun 10;16(2):309-12. Epub 2011 May 10.

Department of Biomedical Engineering and Computational Science, Aalto University, P.O. Box 12200, 00076 AALTO, Espoo, Finland.

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http://dx.doi.org/10.1007/s11325-011-0526-9DOI Listing
June 2012