Publications by authors named "Jani Saunavaara"

56 Publications

Infant and Child MRI: A Review of Scanning Procedures.

Front Neurosci 2021 12;15:666020. Epub 2021 Jul 12.

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland.

Magnetic resonance imaging (MRI) is a safe method to examine human brain. However, a typical MR scan is very sensitive to motion, and it requires the subject to lie still during the acquisition, which is a major challenge for pediatric scans. Consequently, in a clinical setting, sedation or general anesthesia is often used. In the research setting including healthy subjects anesthetics are not recommended for ethical reasons and potential longer-term harm. Here we review the methods used to prepare a child for an MRI scan, but also on the techniques and tools used during the scanning to enable a successful scan. Additionally, we critically evaluate how studies have reported the scanning procedure and success of scanning. We searched articles based on special subject headings from PubMed and identified 86 studies using brain MRI in healthy subjects between 0 and 6 years of age. Scan preparations expectedly depended on subject's age; infants and young children were scanned asleep after feeding and swaddling and older children were scanned awake. Comparing the efficiency of different procedures was difficult because of the heterogeneous reporting of the used methods and the success rates. Based on this review, we recommend more detailed reporting of scanning procedure to help find out which are the factors affecting the success of scanning. In the long term, this could help the research field to get high quality data, but also the clinical field to reduce the use of anesthetics. Finally, we introduce the protocol used in scanning 2 to 5-week-old infants in the FinnBrain Birth Cohort Study, and tips for calming neonates during the scans.
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http://dx.doi.org/10.3389/fnins.2021.666020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311184PMC
July 2021

Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins: A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer.

J Magn Reson Imaging 2021 Jul 5. Epub 2021 Jul 5.

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

Background: Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI).

Purpose: To develop and validate radiomics and kallikrein models for the detection of csPCa.

Study Type: Retrospective.

Population: A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated.

Field Strength/sequence: A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI.

Assessment: In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores.

Statistical Tests: For the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P-value < 0.05 were considered significant.

Results: The highest prediction performance was achieved by IMPROD bpMRI Likert and PI-RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion-derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P-value = 0.306; split 2: AUC = 0.83, P-value = 0.488).

Data Conclusion: The use of radiomics and kallikreins failed to outperform PI-RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains.

Level Of Evidence: 1 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27811DOI Listing
July 2021

Magnetic resonance imaging-guided transurethral ultrasound ablation for benign prostatic hyperplasia: 12-month clinical outcomes of a phase I study.

BJU Int 2021 Jun 23. Epub 2021 Jun 23.

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

Objectives: To investigate the safety and feasibility of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) for the treatment of benign prostatic obstruction (BPO).

Patients And Methods: An investigator-initiated, prospective, registered (NCT03350529), phase I study enrolled men with lower urinary tract symptoms due to benign prostatic hyperplasia in need of surgical intervention. Patients were followed for 12 months after TULSA. Uroflowmetry, prostate-specific antigen (PSA) level, and a comprehensive set of functional questionnaires including the Expanded Prostate cancer Index Composite-26, International Prostate Symptom Score (IPSS) and five-item version of the International Index of Erectile Function were obtained at baseline and every 3 months afterwards. MRI was obtained at baseline, and at 3 and 12 months after TULSA. Medication use before and after TULSA were recorded. Adverse events (AEs) were reported using the Clavien-Dindo classification.

Results: A total of 10 men underwent TULSA with no severe AEs encountered. The baseline median (interquartile range [IQR]) age and prostate volume were 68 (63-72) years and 53 (45-66) mL, respectively. At baseline, six patients were moderately symptomatic and four patients severely symptomatic. Nine patients at baseline were on BPO medication. The median (IQR) improvement in the IPSS was 82%, from 17.5 (15.3-23.0) at baseline to 4.0 (2.3-6.3) at 12 months. Similarly, the median maximum urinary flow rate improved by 101%, from a median (IQR) of 12.4 (8.8-17.6) mL/s at baseline to 21.8 (17.6-26.5) mL/s at 12 months. Improvements were already seen at 3 months. The median prostate volume and PSA reduction at 12 months were 33% and 48%, respectively. There were no changes in continence, sexual, erectile or bowel functions. At 12 months, five out of six men with normal ejaculatory function before TULSA reported normal antegrade ejaculations. All patients taking BPO medication before TULSA discontinued medication after TULSA.

Conclusion: TULSA appears to be a safe and effective treatment for BPO, with promising 12-month follow-up outcomes. Further studies with larger cohorts are needed to confirm the observed results.
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http://dx.doi.org/10.1111/bju.15523DOI Listing
June 2021

Vocal music listening enhances post-stroke language network reorganization.

eNeuro 2021 Jun 17. Epub 2021 Jun 17.

Cognitive Brain Research Unit, Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Finland.

Listening to vocal music has been recently shown to improve language recovery in stroke survivors. The neuroplasticity mechanisms supporting this effect are, however, still unknown. Using data from a three-arm single-blind randomized controlled trial including acute stroke patients (N=38) and a 3-month follow-up, we set out to compare the neuroplasticity effects of daily listening to self-selected vocal music, instrumental music, and audiobooks on both brain activity and structural connectivity of the language network. Using deterministic tractography we show that the 3-month intervention induced an enhancement of the microstructural properties of the left frontal aslant tract (FAT) for the vocal music group as compared to the audiobook group. Importantly, this increase in the strength of the structural connectivity of the left FAT correlated with improved language skills. Analyses of stimulus-specific activation changes showed that the vocal music group exhibited increased activations in the frontal termination points of the left FAT during vocal music listening as compared to the audiobook group from acute to 3-month post-stroke stage. The increased activity correlated with the structural neuroplasticity changes in the left FAT. These results suggest that the beneficial effects of vocal music listening on post-stroke language recovery are underpinned by structural neuroplasticity changes within the language network and extend our understanding of music-based interventions in stroke rehabilitation.Post-stroke language deficits have a devastating effect on patients and their families. Current treatments yield highly variable outcomes and the evidence for their long-term effects is limited. Patients often receive insufficient treatment that are predominantly given outside the optimal time window for brain plasticity. Post-stroke vocal music listening improves language outcome which is underpinned by neuroplasticity changes within the language network. Vocal music listening provides a complementary rehabilitation strategy which could be safely implemented in the early stages of stroke rehabilitation and seems to specifically target language symptoms and recovering language network.
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http://dx.doi.org/10.1523/ENEURO.0158-21.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266215PMC
June 2021

Neonatal amygdala volumes and the development of self-regulation from early infancy to toddlerhood.

Neuropsychology 2021 Mar;35(3):285-299

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku.

At the broadest level, self-regulation (SR) refers to a range of separate, but interrelated, processes (e.g., working memory, inhibition, and emotion regulation) central for the regulation of cognition, emotion, and behavior that contribute to a plethora of health and mental health outcomes. SR skills develop rapidly in early childhood, but their neurobiological underpinnings are not yet well understood. The amygdala is one key structure in negative emotion generation that may disrupt SR. In the current study, we investigated the associations between neonatal amygdala volumes and mother-reported and observed child SR during the first 3 years of life. We expected that larger neonatal amygdala volumes would be related to poorer SR in children. We measured amygdala volumes from magnetic resonance imaging (MRI) performed at age = 3.7 ± 1.0. We examined the associations between the amygdala volumes corrected for intracranial volume (ICV) and (a) parent-reported indicators of SR at 6, 12, and 24 months ( = 102) and (b) observed task-based indicators of SR (working memory and inhibitory control) at 30 months of age in a smaller subset of participants ( = 80). Bilateral neonatal amygdala volumes predicted poorer working memory at 30 months in girls, whereas no association was detected between amygdalae and inhibitory control or parent-reported SR. The left amygdala by sex interaction survived correction for multiple comparisons. Neonatal amygdala volume is associated with working memory, particularly among girls, and the association is observed earlier than in prior studies. Moreover, our findings suggest that the neural correlates for parent-reported, compared to observed early life SR, may differ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000724DOI Listing
March 2021

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 08 13;48(9):2951-2959. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263440PMC
August 2021

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

BMC Sports Sci Med Rehabil 2021 Feb 24;13(1):16. Epub 2021 Feb 24.

Turku PET Centre, University of Turku, P.O. Box 52, FIN-20521, Turku, Finland.

Background: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk.

Methods: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983-1987, 1975-1979, and 1945-1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength.

Discussion: This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors.

Trial Registration: ClinicalTrials.gov , NCT03730610 . Prospectively registered 5 November 2018.
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http://dx.doi.org/10.1186/s13102-021-00241-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905681PMC
February 2021

Feasibility of apparent diffusion coefficient in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids - a comparison with the Funaki classification.

Int J Hyperthermia 2021 ;38(1):85-94

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

Purpose: To investigate the feasibility of using an apparent diffusion coefficient (ADC) classification in predicting the technical outcome of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it to the Funaki classification.

Materials And Methods: Forty-two patients with forty-eight uterine fibroids underwent diffusion-weighted imaging (DWI) before MRgHIFU treatment. The DW images were acquired with five different b-values. Correlations between ADC values and treatment parameters were assessed. Optimal ADC cutoff values were determined to predict technical outcomes, that is, nonperfused volume ratios (NPVr) such that three classification groups were created (NPVr of <30%, 30-80%, or >80%). Results were compared to the Funaki classification using receiver-operating-characteristic (ROC) curve analysis, with statistical significance being tested with the Chi-square test.

Results: A statistically significant negative correlation (Spearman's = -0.31, -value < 0.05) was detected between ADC values and NPV ratios. ROC curve analysis indicated that optimal ADC cutoff values of 980 × 10mm/s (NPVr > 80%) and 1800 × 10mm/s (NPVr < 30%) made it possible to classify fibroids into three groups: ADC I (NPVr > 80%), ADC II (NPVr 30-80%) and ADC III (NPVr < 30%). Analysis of the whole model area under the curve resulted in values of 0.79 for the ADC classification (-value = 0.0007) and 0.62 for the Funaki classification (-value = 0.0527).

Conclusions: Lower ADC values prior to treatment correlate with higher NPV ratios. The ADC classification seems to be able to predict the NPV ratio and may even outperform the Funaki classification. Based on these results DWI and ADC maps should be included in the MRI screening protocol.
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http://dx.doi.org/10.1080/02656736.2021.1874545DOI Listing
July 2021

Acute and subacute prostate MRI findings after MRI-guided transurethral ultrasound ablation of prostate cancer.

Acta Radiol 2020 Nov 28:284185120976931. Epub 2020 Nov 28.

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

Background: Magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) is an emerging method for treatment of localized prostate cancer (PCa). TULSA-related subacute MRI findings have not been previously characterized.

Purpose: To evaluate acute and subacute MRI findings after TULSA treatment in a treat-and-resect setting.

Material And Methods: Six men with newly diagnosed MRI-visible and biopsy-concordant clinically significant PCa were enrolled and completed the study. Eight lesions classified as PI-RADS 3-5 were focally ablated using TULSA. One- and three-week follow-up MRI scans were performed between TULSA and robot-assisted laparoscopic prostatectomy.

Results: TULSA-related hemorrhage was detected as a subtle T1 hyperintensity and more apparent T2 hypointensity in the MRI. Both prostate volume and non-perfused volume (NPV) markedly increased after TULSA at one week and three weeks after treatment, respectively. Lesion apparent diffusion coefficient values increased one week after treatment and decreased nearing the baseline values at the three-week MRI follow-up.

Conclusion: The optimal timing of MRI follow-up seems to be at the earliest at three weeks after treatment, when the post-procedural edema has decreased and the NPV has matured. Diffusion-weighted imaging has little or no added diagnostic value in the subacute setting.
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http://dx.doi.org/10.1177/0284185120976931DOI Listing
November 2020

Association of Cumulative Paternal Early Life Stress With White Matter Maturation in Newborns.

JAMA Netw Open 2020 11 2;3(11):e2024832. Epub 2020 Nov 2.

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Institute of Clinical Medicine, University of Turku, Turku, Finland.

Importance: Early life stress (ELS) has been shown to affect brain development and health outcomes. Recent animal studies have linked paternal early stress exposures with next-generation outcomes. Epigenetic inheritance through the male germline has been suggested to be one of the mechanisms.

Objectives: To test whether paternal ELS, as measured using the Trauma and Distress Scale, is associated with neonate brain development.

Design, Setting, And Participants: This cohort study included data from participants from the prospective 2-generation FinnBrain Birth Cohort, which was collected from 2011 to 2015. Pregnant women and the fathers were consecutively recruited at gestational week 12 from maternity clinics in Finland. Magnetic resonance imaging data were analyzed in 2019. Participants in this study were 72 families (infant, father, mother).

Exposure: Paternal exposure to ELS.

Main Outcomes And Measures: Fractional anisotropy (FA) values in the major white-matter tracts of the newborn brain.

Results: A total of 72 trios (infant, mother, and father) were analyzed. At the time of delivery, the mean (SD) age was 31.0 (4.4) years for fathers and 30.3 (4.5) years for mothers. Forty-one infants (57%) were boys; mean (SD) child age at inclusion was 26.9 (7.2) days from birth and 205 (8) days from estimated conception. Increasing levels of paternal ELS were associated with higher FA values in the newborn brain in the body of the corpus callosum, right superior corona radiata, and retrolenticular parts of the internal capsule. This association persisted after controlling for maternal ELS, maternal socioeconomic status (SES), maternal body mass index, maternal depressive symptoms during pregnancy, child sex, and child age from birth and gestation corrected age when imaged. In additional region-of-interest analyses, the association between FA values and paternal Trauma and Distress Scale sum scores remained statistically significant in the earliest maturing regions of the brain, eg, the genu of the corpus callosum (in the regression models, β = 0.00096; 95% CI, 0.00034-0.00158; P = .003) and the splenium (β = 0.00090; 95% CI, 0.00000-0.00180; P = .049).

Conclusions And Relevance: This cohort study found a statistically significant association between paternal ELS and offspring brain development. This finding may have far-reaching implications in pediatrics, as it suggests the possibility of a novel route of intergenerational inheritance of ELS on next-generation brain development.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.24832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686861PMC
November 2020

Oxytocin selectively reduces blood flow in uterine fibroids without an effect on myometrial blood flow: a dynamic contrast enhanced MRI evaluation.

Int J Hyperthermia 2020 ;37(1):1293-1300

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

Introduction: Uterine fibroids are the most common benign neoplasms in women. The administration of intravenous oxytocin is known to increase the efficacy of a non-invasive thermal ablation method (MR-HIFU) for treating fibroids. However, it is not known whether this phenomenon is caused by the effect of the oxytocin on the myometrium or the fibroid itself. The objective of this study was to evaluate the influence of oxytocin on the blood flow of fibroids, myometrium and skeletal muscle using a quantitative perfusion MRI technique.

Materials And Methods: 17 premenopausal women with fibroids considered to be treated with MR-HIFU and 11 women with no fibroids were enrolled in the study. An extended MRI protocol of the pelvis was acquired for each subject. Later another MRI scan was performed with continuous intravenous infusion of oxytocin. The effect of oxytocin was analyzed from quantitative perfusion imaging. The study was registered in clinicaltrials.gov NCT03937401.

Results: Oxytocin decreased the blood flow of each fibroid; the median blood flow of fibroid was 39.9 ml/100 g tissue/min without and 3.5 mL/100 g/min with oxytocin ( ≤ 0.0001). Oxytocin did not affect the blood flow of the myometrium in either group. Oxytocin increased the blood flow of the skeletal muscle in both groups ( = 0.04).

Conclusion: Oxytocin is effective in decreasing the blood flow in fibroids while having minor or no effect on the blood flow of normal myometrium. Routine use of oxytocin in HIFU therapy may make the therapy suitable to a larger group of women in a safe manner.
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http://dx.doi.org/10.1080/02656736.2020.1846792DOI Listing
June 2021

Vocal music enhances memory and language recovery after stroke: pooled results from two RCTs.

Ann Clin Transl Neurol 2020 11 6;7(11):2272-2287. Epub 2020 Oct 6.

Cognitive Brain Research Unit, Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Objective: Previous studies suggest that daily music listening can aid stroke recovery, but little is known about the stimulus-dependent and neural mechanisms driving this effect. Building on neuroimaging evidence that vocal music engages extensive and bilateral networks in the brain, we sought to determine if it would be more effective for enhancing cognitive and language recovery and neuroplasticity than instrumental music or speech after stroke.

Methods: Using data pooled from two single-blind randomized controlled trials in stroke patients (N = 83), we compared the effects of daily listening to self-selected vocal music, instrumental music, and audiobooks during the first 3 poststroke months. Outcome measures comprised neuropsychological tests of verbal memory (primary outcome), language, and attention and a mood questionnaire performed at acute, 3-month, and 6-month stages and structural and functional MRI at acute and 6-month stages.

Results: Listening to vocal music enhanced verbal memory recovery more than instrumental music or audiobooks and language recovery more than audiobooks, especially in aphasic patients. Voxel-based morphometry and resting-state and task-based fMRI results showed that vocal music listening selectively increased gray matter volume in left temporal areas and functional connectivity in the default mode network.

Interpretation: Vocal music listening is an effective and easily applicable tool to support cognitive recovery after stroke as well as to enhance early language recovery in aphasia. The rehabilitative effects of vocal music are driven by both structural and functional plasticity changes in temporoparietal networks crucial for emotional processing, language, and memory.
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http://dx.doi.org/10.1002/acn3.51217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664275PMC
November 2020

Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder.

J Neurosci Res 2020 12 9;98(12):2529-2540. Epub 2020 Sep 9.

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland.

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.
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http://dx.doi.org/10.1002/jnr.24722DOI Listing
December 2020

Palliative MRI-guided transurethral ultrasound ablation for symptomatic locally advanced prostate cancer.

Scand J Urol 2020 Dec 8;54(6):481-486. Epub 2020 Sep 8.

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

Purpose: Locally advanced prostate cancer can cause bladder outlet obstruction, gross hematuria and frequent hospitalization. While these complications are commonly treated by palliative transurethral resection of the prostate, the improvement is often insufficient. The purpose of this study was to evaluate the safety and feasibility of MRI-guided transurethral ultrasound ablation as an alternative palliative treatment option (pTULSA) for men suffering from symptomatic locally advanced prostate cancer.

Methods: This prospective, phase one study included 10 men in need of palliative surgical intervention due to urinary retention and gross hematuria caused by locally advanced prostate cancer. Patients were followed for 1 year at 3-month intervals. Time without catheter, time without hematuria, reduction in hospitalization time, and adverse events were measured.

Results: Ten patients with locally advanced prostate cancer were enrolled, all having continuous catheterization due to urinary retention and nine had gross hematuria before treatment. At 1 week post-pTULSA five patients were catheter-free. At last follow-up catheter-free and gross hematuria-free rates were 70% and 100%, respectively. Average hospitalization time from local complications reduced from 7.3 to 1.4 days in the 6 months before and after pTULSA. No > Grade 2 treatment related adverse events were reported, with all five being urinary tract infections.

Conclusions: pTULSA appears safe and feasible for palliative ablation of locally advanced prostate cancer. The therapy seems to accomplish long-term hematuria control, can relieve bladder outlet obstruction in selected patients, and seems to reduce the burden of hospitalization due to local complications. NCT03350529.
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http://dx.doi.org/10.1080/21681805.2020.1814857DOI Listing
December 2020

Newborn left amygdala volume associates with attention disengagement from fearful faces at eight months.

Dev Cogn Neurosci 2020 10 15;45:100839. Epub 2020 Aug 15.

The FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Institute of Clinical Medicine, University of Turku, Finland; Department of Psychiatry, Turku University Hospital, University of Turku, Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Finland.

After 5 months of age, infants begin to prioritize attention to fearful over other facial expressions. One key proposition is that amygdala and related early-maturing subcortical network, is important for emergence of this attentional bias - however, empirical data to support these assertions are lacking. In this prospective longitudinal study, we measured amygdala volumes from MR images in 65 healthy neonates at 2-5 weeks of gestation corrected age and attention disengagement from fearful vs. non-fearful facial expressions at 8 months with eye tracking. Overall, infants were less likely to disengage from fearful than happy/neutral faces, demonstrating an age-typical bias for fear. Left, but not right, amygdala volume (corrected for intracranial volume) was positively associated with the likelihood of disengaging attention from fearful faces to a salient lateral distractor (r = .302, p = .014). No association was observed with the disengagement from neutral or happy faces in equivalent conditions (r = .166 and .125, p = .186 and .320, respectively). These results are the first to link the amygdala volume with the emerging perceptual vigilance for fearful faces during infancy. They suggest a link from the prenatally defined variability in the amygdala size to early postnatal emotional and social traits.
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http://dx.doi.org/10.1016/j.dcn.2020.100839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451600PMC
October 2020

Newborn amygdalar volumes are associated with maternal prenatal psychological distress in a sex-dependent way.

Neuroimage Clin 2020 11;28:102380. Epub 2020 Aug 11.

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Institute of Clinical Medicine University of Turku, Turku, Finland; Department of Psychiatry, University of Turku and Turku University Hospital, Turku, Finland; Center for Population Health Research, University of Turku and Turku University Hospital, Finland.

Maternal psychological distress during pregnancy (PPD) has been associated with changes in offspring amygdalar and hippocampal volumes. Studies on child amygdalae suggest that sex moderates the vulnerability of fetal brains to prenatal stress. However, this has not yet been observed in these structures in newborns. Newborn studies are crucial, as they minimize the confounding influence of postnatal life. We investigated the effects of maternal prenatal psychological symptoms on newborn amygdalar and hippocampal volumes and their interactions with newborn sex in 123 newborns aged 2-5 weeks (69 males, 54 females). Based on earlier studies, we anticipated small, but statistically significant effects of PPD on the volumes of these structures. Maternal psychological distress was measured at gestational weeks (GW) 14, 24 and 34 using Symptom Checklist-90 (SCL-90, anxiety scale) and Edinburgh Postnatal Depression Scale (EPDS) questionnaires. Newborn sex was found to moderate the relationship between maternal distress symptoms at GW 24 and the volumes of left and right amygdala. This relationship was negative and significant only in males. No significant main effect or sex-based moderation was found for hippocampal volumes. This newborn study provides evidence for a sex-dependent influence of maternal psychiatric symptoms on amygdalar structural development. This association may be relevant to later psychopathology.
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http://dx.doi.org/10.1016/j.nicl.2020.102380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453059PMC
June 2021

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

Newborn white matter microstructure moderates the association between maternal postpartum depressive symptoms and infant negative reactivity.

Soc Cogn Affect Neurosci 2020 07;15(6):649-660

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland.

Maternal postpartum depression is a prominent risk factor for aberrant child socioemotional development, but there is little understanding about the neural phenotypes that underlie infant sensitivity to maternal depression. We examined whether newborn white matter fractional anisotropy (FA), a measure of white matter maturity, moderates the association between maternal postpartum depressive symptoms and infant negative reactivity at 6 months. Participants were 80 mother-infant dyads participating in a prospective population-based cohort, and included families whose newborns underwent a magnetic resonance/diffusion tensor imaging scan at 2-5 weeks of age and whose mothers reported their own depressive symptoms at 3 and 6 months postpartum and infant negative emotional reactivity at 6 months. The whole-brain FA moderated the association between maternal depressive symptoms and mother-reported infant negative reactivity at 6 months after adjusting for the covariates. Maternal depressive symptoms were positively related to infant negative reactivity among infants with high or average FA in the whole brain and in corpus callosum and cingulum, but not among those with low FA. The link between maternal depressive symptoms and infant negative reactivity was moderated by newborn FA. The variation in white matter microstructure might play a role in child susceptibility to parental distress.
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http://dx.doi.org/10.1093/scan/nsaa081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393309PMC
July 2020

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

Negative Predictive Value of Biparametric Prostate Magnetic Resonance Imaging in Excluding Significant Prostate Cancer: A Pooled Data Analysis Based on Clinical Data from Four Prospective, Registered Studies.

Eur Urol Focus 2021 May 14;7(3):522-531. Epub 2020 May 14.

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

Background: Multiparametric prostate magnetic resonance imaging (mpMRI) can be considered the gold standard in prostate magnetic resonance imaging (MRI). Biparametric prostate MRI (bpMRI) is faster and could be a feasible alternative to mpMRI.

Objective: To determine the negative predictive value (NPV) of Improved Prostate Cancer Diagnosis (IMPROD) bpMRI as a whole and in clinical subgroups in primary diagnostics of clinically significant prostate cancer (CSPCa).

Design, Setting, And Participants: This is a pooled data analysis of four prospective, registered clinical trials investigating prebiopsy IMPROD bpMRI. Men with a clinical suspicion of prostate cancer (PCa) were included.

Intervention: Prebiopsy IMPROD bpMRI was performed, and an IMPROD bpMRI Likert scoring system was used. If suspicious lesions (IMPROD bpMRI Likert score 3-5) were visible, targeted biopsies in addition to systematic biopsies were taken.

Outcome Measurements And Statistical Analysis: Performance measures of IMPROD bpMRI in CSPCa diagnostics were evaluated. NPV was also evaluated in clinical subgroups. Gleason grade ≥3 + 4 in any biopsy core taken was defined as CSPCa.

Results And Limitations: A total of 639 men were included in the analysis. The mean age was 64 yr, mean prostate-specific antigen level was 8.9 ng/ml, and CSPCa prevalence was 48%. NPVs of IMPROD bpMRI Likert scores 3-5 and 4-5 for CSPCa were 0.932 and 0.909, respectively, and the corresponding positive predictive values were 0.589 and 0.720. Only nine of 132 (7%) men with IMPROD bpMRI Likert score 1-2 had CSPCa and none with Gleason score >7. Thus, 132 of 639 (21%) study patients could have avoided biopsies without missing a single Gleason >7 cancer in the study biopsies. In the subgroup analysis, no clear outlier was present. The limitation is uncertainty of the true CSPCa prevalence.

Conclusions: IMPROD bpMRI demonstrated a high NPV to rule out CSPCa. IMPROD bpMRI Likert score 1-2 excludes Gleason >7 PCa in the study biopsies.

Patient Summary: We investigated the feasibility of prostate magnetic resonance imaging (MRI) with the Improved Prostate Cancer Diagnosis (IMPROD) biparametric MRI (bpMRI) protocol in excluding significant prostate cancer. In this study, highly aggressive prostate cancer was excluded using the publicly available IMPROD bpMRI protocol (http://petiv.utu.fi/multiimprod/).
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http://dx.doi.org/10.1016/j.euf.2020.04.007DOI Listing
May 2021

Resting-state networks of the neonate brain identified using independent component analysis.

Dev Neurobiol 2020 03 19;80(3-4):111-125. Epub 2020 Apr 19.

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Institute of Clinical Medicine, University of Turku, Turku, Finland.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6-min resting-state data set acquired from 21 naturally sleeping term-born (age 26 ± 6.7 d), healthy neonates to investigate the emerging functional resting-state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default-mode-network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA-based denoising of fMRI data increased the number of networks identified with group-ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth.
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http://dx.doi.org/10.1002/dneu.22742DOI Listing
March 2020

Prevalence and Risk Factors of Incidental Findings in Brain MRIs of Healthy Neonates-The FinnBrain Birth Cohort Study.

Front Neurol 2019 8;10:1347. Epub 2020 Jan 8.

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Institute of Clinical Medicine, University of Turku, Turku, Finland.

Birth is a traumatic event with molding forces directed to the fetal skull, which may result in intracranial hemorrhages. However, the knowledge on prevalence and risk factors of incidental brain magnetic resonance imaging (MRI) findings in infants is still inconclusive. The prevalence and nature of incidental MRI findings were assessed in a birth cohort of 175 asymptomatic infants. The role of delivery method as well as other potential risk factors for intracranial hemorrhages were evaluated. The infants underwent 3T MRI at the age of 2-5 weeks, and the neurological status of the infants with an incidental finding was evaluated by a pediatric neurologist. Information on the delivery method, duration of delivery, parity, used anesthesia, oxytocin induction, and Apgar score was gathered to evaluate their association with the prevalence of hemorrhages. Incidental intracranial hemorrhages were detected in 12 infants (6.9%), all following spontaneous or assisted vaginal delivery. Vacuum-assistance was found to be a risk factor for subdural hemorrhages with an odds ratio (OR) of 4.7 (95% CI [1.18; 18.9], = 0.032). All infants were evaluated to develop normally by their clinical status. Incidental intracranial hemorrhages are relatively common among infants born by vaginal delivery. They are often of little clinical significance within the first years of life and have unlikely consequences for later neurodevelopment either. Despite their benign character, investigators should be prepared to share this information with parents competently as the findings can cause parental anxiety, and especially as the popularity of MRI as a research tool is increasing.
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http://dx.doi.org/10.3389/fneur.2019.01347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960102PMC
January 2020

Qualitative and Quantitative Reporting of a Unique Biparametric MRI: Towards Biparametric MRI-Based Nomograms for Prediction of Prostate Biopsy Outcome in Men With a Clinical Suspicion of Prostate Cancer (IMPROD and MULTI-IMPROD Trials).

J Magn Reson Imaging 2020 05 21;51(5):1556-1567. Epub 2019 Nov 21.

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

Background: Multiparametric MRI of the prostate has been shown to improve the risk stratification of men with an elevated prostate-specific antigen (PSA). However, long acquisition time, high cost, and inter-center/reader variability of a routine prostate multiparametric MRI limit its wider adoption.

Purpose: To develop and validate nomograms based on unique rapid biparametric MRI (bpMRI) qualitative and quantitative derived variables for prediction of clinically significant cancer (SPCa).

Study Type: Retrospective analyses of single (IMPROD, NCT01864135) and multiinstitution trials (MULTI-IMPROD, NCT02241122).

Population: 161 and 338 prospectively enrolled men who completed the IMPROD and MULTI-IMPROD trials, respectively.

Field Strength/sequence: IMPROD bpMRI: 3T/1.5T, T -weighted imaging, three separate diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm ; 2) b values 0, 1500 s/mm ; 3) values 0, 2000 s/mm .

Assessment: The primary endpoint of the combined trial analysis was the diagnostic accuracy of the combination of IMPROD bpMRI and clinical variables for detection of SPCa.

Statistical Tests: Logistic regression models were developed using IMPROD trial data and validated using MULTI-IMPROD trial data. The model's performance was expressed as the area under the curve (AUC) values for the detection of SPCa, defined as ISUP Gleason Grade Group ≥2.

Results: A model incorporating clinical variables had an AUC (95% confidence interval) of 0.83 (0.77-0.89) and 0.80 (0.75-0.85) in the development and validation cohorts, respectively. The corresponding values for a model using IMPROD bpMRI findings were 0.93 (0.89-0.97), and 0.88 (0.84-0.92), respectively. Further addition of the quantitative DWI-based score did not improve AUC values (P < 0.05).

Data Conclusion: A prediction model using qualitative IMPROD bpMRI findings demonstrated high accuracy for predicting SPCa in men with an elevated PSA. Online risk calculator: http://petiv.utu.fi/multiimprod/ Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1556-1567.
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http://dx.doi.org/10.1002/jmri.26975DOI Listing
May 2020

Repeatability of radiomics and machine learning for DWI: Short-term repeatability study of 112 patients with prostate cancer.

Magn Reson Med 2020 06 8;83(6):2293-2309. Epub 2019 Nov 8.

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

Purpose: To evaluate repeatability of prostate DWI-derived radiomics and machine learning methods for prostate cancer (PCa) characterization.

Methods: A total of 112 patients with diagnosed PCa underwent 2 prostate MRI examinations (Scan1 and Scan2) performed on the same day. DWI was performed using 12 b-values (0-2000 s/mm ), post-processed using kurtosis function, and PCa areas were annotated using whole mount prostatectomy sections. A total of 1694 radiomic features including Sobel, Kirch, Gradient, Zernike Moments, Gabor, Haralick, CoLIAGe, Haar wavelet coefficients, 3D analogue to Laws features, 2D contours, and corner detectors were calculated. Radiomics and 4 feature pruning methods (area under the receiver operator characteristic curve, maximum relevance minimum redundancy, Spearman's ρ, Wilcoxon rank-sum) were evaluated in terms of Scan1-Scan2 repeatability using intraclass correlation coefficient (ICC)(3,1). Classification performance for clinically significant and insignificant PCa with Gleason grade groups 1 versus >1 was evaluated by area under the receiver operator characteristic curve in unseen random 30% data split.

Results: The ICC(3,1) values for conventional radiomics and feature pruning methods were in the range of 0.28-0.90. The machine learning classifications varied between Scan1 and Scan2 with % of same class labels between Scan1 and Scan2 in the range of 61-81%. Surface-to-volume ratio and corner detector-based features were among the most represented features with high repeatability, ICC(3,1) >0.75, consistently high ranking using all 4 feature pruning methods, and classification performance with area under the receiver operator characteristic curve >0.70.

Conclusion: Surface-to-volume ratio and corner detectors for prostate DWI led to good classification of unseen data and performed similarly in Scan1 and Scan2 in contrast to multiple conventional radiomic features.
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http://dx.doi.org/10.1002/mrm.28058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047644PMC
June 2020

A Novel Approach for Manual Segmentation of the Amygdala and Hippocampus in Neonate MRI.

Front Neurosci 2019 24;13:1025. Epub 2019 Sep 24.

FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Institute of Clinical Medicine, University of Turku, Turku, Finland.

The gross anatomy of the infant brain at term is fairly similar to that of the adult brain, but structures are immature, and the brain undergoes rapid growth during the first 2 years of life. Neonate magnetic resonance (MR) images have different contrasts compared to adult images, and automated segmentation of brain magnetic resonance imaging (MRI) can thus be considered challenging as less software options are available. Despite this, most anatomical regions are identifiable and thus amenable to manual segmentation. In the current study, we developed a protocol for segmenting the amygdala and hippocampus in T2-weighted neonatal MR images. The participants were 31 healthy infants between 2 and 5 weeks of age. Intra-rater reliability was measured in 12 randomly selected MR images, where 6 MR images were segmented at 1-month intervals between the delineations, and another 6 MR images at 6-month intervals. The protocol was also tested by two independent raters in 20 randomly selected T2-weighted images, and finally with T1 images. Intraclass correlation coefficient (ICC) and Dice similarity coefficient (DSC) for intra-rater, inter-rater, and T1 vs. T2 comparisons were computed. Moreover, manual segmentations were compared to automated segmentations performed by iBEAT toolbox in 10 T2-weighted MR images. The intra-rater reliability was high ICC ≥ 0.91, DSC ≥ 0.89, the inter-rater reliabilities were satisfactory ICC ≥ 0.90, DSC ≥ 0.75 for hippocampus and DSC ≥ 0.52 for amygdalae. Segmentations for T1 vs. T2-weighted images showed high consistency ICC ≥ 0.90, DSC ≥ 0.74. The manual and iBEAT segmentations showed no agreement, DSC ≥ 0.39. In conclusion, there is a clear need to improve and develop the procedures for automated segmentation of infant brain MR images.
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http://dx.doi.org/10.3389/fnins.2019.01025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768976PMC
September 2019

Prostate Cancer Risk Stratification in Men With a Clinical Suspicion of Prostate Cancer Using a Unique Biparametric MRI and Expression of 11 Genes in Apparently Benign Tissue: Evaluation Using Machine-Learning Techniques.

J Magn Reson Imaging 2020 05 6;51(5):1540-1553. Epub 2019 Oct 6.

Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland.

Background: Accurate risk stratification of men with a clinical suspicion of prostate cancer (cSPCa) remains challenging despite the increasing use of MRI.

Purpose: To evaluate the diagnostic accuracy of a unique biparametric MRI protocol (IMPROD bpMRI) combined with clinical and molecular markers in men with cSPCa.

Study Type: Prospective single-institutional clinical trial (NCT01864135).

Subjects: Eighty men with cSPCa.

Field Strength/sequence: 3T, surface array coils. Two T -weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm ; 2) b-values 0,1500 s/mm ; 3) b-values 0, 2000 s/mm .

Assessment: IMPROD bpMRI examinations were qualitatively (IMPROD bpMRI Likert score) and quantitatively (DWI-based Gleason grade score) prospectively reported. Men with IMPROD bpMRI Likert 3-5 had two targeted biopsies followed by 12-core systematic biopsies (SB); those with IMPROD bpMRI Likert 1-2 had only SB. Additionally, 2-core from normal-appearing prostate areas were obtained for the mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 measured by quantitative reverse-transcription polymerase chain reaction.

Statistical Tests: Univariate and multivariate analysis using regularized least-squares, feature selection and tournament leave-pair-out cross-validation (TLPOCV), as well as 10 random splits of the data in training-testing sets, were used to evaluate the mRNA, clinical and IMPROD bpMRI parameters in detecting clinically significant prostate cancer (SPCa) defined as Gleason score ≥ 3 + 4. The evaluation metric was the area under the curve (AUC).

Results: IMPROD bpMRI Likert demonstrated the highest TLPOCV AUC of 0.92. The tested clinical variables had AUC 0.56-0.73, while the mRNA and additional IMPROD bpMRI parameters had AUC 0.50-0.67 and 0.65-0.89 respectively. The combination of clinical and mRNA biomarkers produced TLPOCV AUC of 0.87, the highest TLPOCV performance without including IMPROD bpMRI Likert.

Data Conclusion: The qualitative IMPROD bpMRI Likert score demonstrated the highest accuracy for SPCa detection compared with the tested clinical variables and mRNA biomarkers.

Level Of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1540-1553.
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http://dx.doi.org/10.1002/jmri.26945DOI Listing
May 2020

Feasibility of MRI-guided transurethral ultrasound for lesion-targeted ablation of prostate cancer.

Scand J Urol 2019 Oct 26;53(5):295-302. Epub 2019 Sep 26.

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

MRI-guided transurethral ultrasound ablation (TULSA) has been evaluated for organ-confined prostate cancer (PCa). The purpose of this study was to assess the safety and toxicity, accuracy and short-term evolution of cell-death after lesion-targeted TULSA. This prospective, registered, Phase-I treat-and-3-week-resect-study enrolled six patients with MRI-visible-biopsy-concordant PCa. Lesions were targeted using TULSA with radical intent, except near neurovascular bundles (NVB). Robot-assisted-laparoscopic-prostatectomy (RALP) was performed at 3 weeks. Post-TULSA assessments included MRI (1 and 3 weeks), adverse events and quality-of-life (QoL) to 3 weeks, followed by RALP and whole-mount-histology. Treatment accuracy and demarcation of thermal injury were assessed using MRI and histology. Six patients (median age = 70 years, prostate volume = 60 ml, PSA = 8.9 ng/ml) with eight biopsy-confirmed MRI-lesions (PIRADS ≥3) were TULSA-treated without complications (median sonication and MRI-times of 17 and 117 min). Foley-catheter removal was uneventful at 2-3 days. Compared to baseline, no differences in QoL were noted at 3 weeks. During follow-up, MRI-derived non-perfused-volume covered ablated targets and increased 36% by 3 weeks, correlating with necrosis-area on histology. Mean histological demarcation between complete necrosis and outer-limit-of-thermal-injury was 1.7 ± 0.4 mm. Coagulation necrosis extended to capsule except near NVB, where 3 mm safety-margins were applied. RALPs were uncomplicated and histopathology showed no viable cancer within the ablated tumor-containing target. Lesion-targeted TULSA demonstrates accurate and safe ablation of PCa. A significant increase of post-TULSA non-perfused-volume was observed during 3 weeks follow-up concordant with necrosis on histology. TULSA achieved coagulation necrosis of all targeted tissues. A limitation of this treat-and-resect-study-design was conservative treatment near NVB in patients scheduled for RALP.
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http://dx.doi.org/10.1080/21681805.2019.1660707DOI Listing
October 2019

Prebiopsy IMPROD Biparametric Magnetic Resonance Imaging Combined with Prostate-Specific Antigen Density in the Diagnosis of Prostate Cancer: An External Validation Study.

Eur Urol Oncol 2020 10 6;3(5):648-656. Epub 2019 Sep 6.

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

Background: Biparametric magnetic resonance imaging (bpMRI) combined with prostate-specific antigen density (PSAd) may be an effective strategy for selecting men for prostate biopsy. It has been shown that performing biopsy only for men with bpMRI Likert scores of 4-5 or PSAd ≥0.15 ng/ml/cm is the most efficient strategy.

Objective: To externally validate previously published biopsy strategies using two prospective bpMRI trial cohorts.

Design, Setting, And Participants: After IMPROD bpMRI, 499 men had systematic transrectal prostate biopsies and men with IMPROD bpMRI Likert scores of 3-5 had an additional two to four targeted biopsies.

Outcome Measurements And Statistical Analysis: Various IMPROD bpMRI Likert score and PSAd thresholds were assessed using detection rates for significant prostate cancer (sPCa; Gleason score ≥3 + 4), predictive values, and proportion of biopsies avoided. Net benefits and decision curve analyses (DCA) were compared with the aim of finding an optimal strategy for sPCa detection. Combined biopsies were used for reference.

Results And Limitations: The negative predictive value (NPV) for sPCa in IMPROD bpMRI Likert 3-5 and 4-5 score groups was 93% and 92%, respectively, while the corresponding positive predictive value (PPV) was 57% and 72%, respectively. In DCA, the optimal combination was IMPROD bpMRI Likert score 4-5 or Likert 3 with PSAd ≥0.20 ng/ml/cm, which had NPV of 93% and PPV of 67%. Using this combination, 35% of the study patients would have avoided biopsies and 13 sPCas (6%, 13/229, of all sPCas diagnosed) would have been missed.

Conclusions: IMPROD bpMRI demonstrated a good NPV for sPCa. PSAd improved the NPV mainly among men with equivocal suspicion on IMPROD bpMRI. However, the additional value of PSAd was marginal: the NPV and PPV for IMPROD bpMRI Likert 4-5 score group were 92% and 72%, respectively, while the corresponding values for the best combination strategy were 93% and 67%.

Patient Summary: We investigated a rapid prostate magnetic resonance imaging protocol (IMPROD bpMRI) combined with prostate-specific antigen (PSA) density for detection of significant prostate cancer. Our results show that IMPROD bpMRI is a good diagnostic tool, but the additional value provided by PSA density is marginal.
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http://dx.doi.org/10.1016/j.euo.2019.08.008DOI Listing
October 2020

Histopathological evaluation of prostate specimens after thermal ablation may be confounded by the presence of thermally-fixed cells.

Int J Hyperthermia 2019 ;36(1):915-925

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

Prostate cancer can be eradicated with heat exposure. However, high and rapid temperature elevations may cause thermofixation giving the appearance of viable tissue. The purpose was to characterize the immunoprofile and evaluate the viability of prostate regions with suspected thermofixation. A prospective, ethics-approved and registered study (NCT03350529) enrolled six patients with MRI-visible, biopsy-concordant prostate cancer to undergo lesion-targeted MRI-guided transurethral ultrasound ablation (TULSA) followed by radical prostatectomy at 3 weeks, to evaluate the accuracy and efficacy of TULSA with whole-mount histology as a reference standard. If ambiguity about complete necrosis within the ablated region remained after hematoxylin-eosin staining, viability was assessed by immunohistochemistry. Treatment day MRI-thermometry and 3-week contrast-enhanced MRI post-TULSA were examined to assess ablation success and correlation with histopathology. One patient presented with an apparently viable subregion inside the ablated area, surrounded by necrosis on H&E staining, located where temperature was highest on MRI-thermometry and tissues completely devascularized on MRI. Immunoprofile of the apparently viable tissue revealed changes in staining patterns suggesting thermofixation; the most significant evidence was the negative cytokeratin 8 staining detected with Cam5.2 antibody. A comprehensive literature review supports these observations of thermofixation with similar findings in prostate and other tissues. Thermally-fixed cells can sustain morphology on H&E staining. Misinterpretation of treatment failure may occur, if this phenomenon is not recognized and immunohistochemistry performed. Based on the previous literature and the current study, Cam5.2 staining for cytokeratin 8 appears to be a practical and reliable tool for distinguishing thermally-fixed from viable cells.
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http://dx.doi.org/10.1080/02656736.2019.1652773DOI Listing
January 2020

Validation of IMPROD biparametric MRI in men with clinically suspected prostate cancer: A prospective multi-institutional trial.

PLoS Med 2019 06 3;16(6):e1002813. Epub 2019 Jun 3.

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

Background: Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption.

Methods And Findings: The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score ≥ 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings.

Conclusions: IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial.

Trial Registration: ClinicalTrials.gov NCT02241122.
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http://dx.doi.org/10.1371/journal.pmed.1002813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546206PMC
June 2019
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