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Background and purpose The diagnostic accuracy of new imaging techniques requires validation, preferably by histopathological verification. The aim of this study was to develop and present a registration procedure between histopathology and in-vivo magnetic resonance imaging (MRI) of the prostate, to estimate its uncertainty and to evaluate the benefit of adding a contour-correcting registration. Materials and methods For twenty-five prostate cancer patients, planned for radical prostatectomy, a 3D-printed prostate mold based on in-vivo MRI was created and an ex-vivo MRI of the specimen, placed inside the mold, was performed. Each histopathology slice was registered to its corresponding ex-vivo MRI slice using a 2D-affine registration. The ex-vivo MRI was rigidly registered to the in-vivo MRI and the resulting transform was applied to the histopathology stack. A 2D deformable registration was used to correct for specimen distortion concerning the specimen’s fit inside the mold. We estimated the spatial uncertainty by comparing positions of landmarks in the in-vivo MRI and the corresponding registered histopathology stack. Results Eighty-four landmarks were identified, located in the urethra (62%), prostatic cysts (33%), and the ejaculatory ducts (5%). The median number of landmarks was 3 per patient. We showed a median in-plane error of 1.8 mm before and 1.7 mm after the contour-correcting deformable registration. In patients with extraprostatic margins, the median in-plane error improved from 2.1 mm to 1.8 mm after the contour-correcting deformable registration. Conclusions Our registration procedure accurately registers histopathology to in-vivo MRI, with low uncertainty. The contour-correcting registration was beneficial in patients with extraprostatic surgical margins.

Purpose Hereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters. Methods Forty-eight patients with genetically verified ATTRv type-A fibril composition, positive 99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPDload) was correlated with echocardiographic strain values and cardiac biomarkers. Results Statistically significant correlations were seen in VOIs between DPD uptakes and the corresponding echocardiographic strain values. Furthermore, DPDload had a strong correlation with echocardiographic strain parameters and also correlated with biomarkers troponin T and logarithmic NT-ProBNP. Conclusions In patients with ATTRv cardiomyopathy, DPD SPECT/CT measures the amyloid distribution and provides information on cardiac amyloid load. DPD amyloid load correlates with functional cardiac parameters.

Background: Hereditary transthyretin amyloid (ATTRv) is a systemic amyloidosis with mainly neurological and cardiac symptoms. The aim of this study was to evaluate the outcome of [18F]Flutemetamol PET/CT-scan of the heart in long-term survivors with ATTRV30M amyloidosis. Methods: Twenty-one patients with ATTRV30M amyloidosis and predominantly neurological symptoms, mainly negative on cardiac 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD)-scintigraphy, were examined with a dynamic [18F]Flutemetamol PET/CT-scan. Five patients suffering from Alzheimer’s disease and one healthy individual served as controls. Volumes of interests were drawn over the intraventricular septum, lateral wall of the left ventricle and free wall of the right ventricle. Clinical records were reviewed for data from previous completed DPD-scintigraphy of the heart and echocardiography. Results: Patients with ATTRv amyloidosis had a higher cardiac uptake than the control-group in all analysed regions of the heart and could be identified with high accuracy (sensitivity 88%, specificity 100%) in static image acquisition at 30 or 60 min. We found no correlation between cardiac [18F]Flutemetamol uptake and clinical variables. Conclusion: In this small study of selected patients, cardiac [18F]Flutemetamol PET/CT could differentiate between healthy individuals and patients with ATTRV30M. [18F]Flutemetamol PET/CT imaging of amyloidosis in patients with a negative DPD-scintigraphy has a potential as a diagnostic method.

Striatal dopamine is involved in facilitation of motor action as well as various cognitive and emotional functions. Positron emission tomography (PET) is the primary imaging method used to investigate dopamine function in humans. Previous PET studies have shown striatal dopamine release during simple finger tapping in both the putamen and the caudate. It is likely that dopamine release in the putamen is related to motor processes while dopamine release in the caudate could signal sustained cognitive component processes of the task, but the poor temporal resolution of PET has hindered firm conclusions. In this study we simultaneously collected [11C]Raclopride PET and functional Magnetic Resonance Imaging (fMRI) data while participants performed finger tapping, with fMRI being able to isolate activations related to individual tapping events. The results revealed fMRI-PET overlap in the bilateral putamen, which is consistent with a motor component process. Selective PET responses in the caudate, ventral striatum, and right posterior putamen, were also observed but did not overlap with fMRI responses to tapping events, suggesting that these reflect non-motor component processes of finger tapping. Our findings suggest an interplay between motor and non-motor-related dopamine release during simple finger tapping and illustrate the potential of hybrid PET-fMRI in revealing distinct component processes of cognitive functions.

Episodic memory is a polygenic trait influenced by different molecular mechanisms. We used PET and a candidate gene approach to investigate how individual differences at the molecular level translate into between-person differences in episodic memory performance of elderly persons. Specifically, we examined the interactive effects between hippocampal dopamine D2 receptor (D2DR) availability and candidate genes relevant for hippocampus-related memory functioning. We show that the positive effects of high D2DR availability in the hippocampus on episodic memory are confined to carriers of advantageous genotypes of the brain-derived neurotrophic factor ( BDNF, rs6265) and the kidney and brain expressed protein ( KIBRA, rs17070145) polymorphisms. By contrast, these polymorphisms did not modulate the positive relationship between caudate D2DR availability and episodic memory.

Normal brain aging is a multidimensional process that includes deterioration in various brain structures and functions, with large heterogeneity in patterns and rates of decline. Sex differences have been reported for various cognitive and brain parameters, but little is known in relation to neuromodulatory aspects of brain aging. We examined sex differences in dopamine D2-receptor (D2DR) availability in relation to episodic memory, but also, grey-matter volumes, white-matter lesions, and cerebral perfusion in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging study. Women had higher D2DR availability in midbrain and left caudate and putamen, as well as superior episodic memory performance. Controlling for left caudate D2DR availability attenuated sex differences in memory performance. In men, lower left caudate D2DR levels were associated with lower cortical perfusion and higher burden of white-matter lesions, as well as with episodic memory performance. However, sex was not a significant moderator of the reported links to D2DR levels. Our findings suggest that sex differences in multiple associations among DA receptor availability, vascular factors, and structural connectivity contribute to sex differences in episodic memory. Future longitudinal studies need to corroborate these patterns by lead-lag associations. This manuscript is part of the Special Issue entitled ‘Cognitive Neuroscience of Healthy and Pathological Aging’ edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP .

Background Attenuation correction of PET/MRI is a remaining problem for whole-body PET/MRI. The statistical decomposition algorithm (SDA) is a probabilistic atlas-based method that calculates synthetic CTs from T2-weighted MRI scans. In this study, we evaluated the application of SDA for attenuation correction of PET images in the pelvic region. Materials and method Twelve patients were retrospectively selected from an ongoing prostate cancer research study. The patients had same-day scans of [11C]acetate PET/MRI and CT. The CT images were non-rigidly registered to the PET/MRI geometry, and PET images were reconstructed with attenuation correction employing CT, SDA-generated CT, and the built-in Dixon sequence-based method of the scanner. The PET images reconstructed using CT-based attenuation correction were used as ground truth. Results The mean whole-image PET uptake error was reduced from − 5.4% for Dixon-PET to − 0.9% for SDA-PET. The prostate standardized uptake value (SUV) quantification error was significantly reduced from − 5.6% for Dixon-PET to − 2.3% for SDA-PET. Conclusion Attenuation correction with SDA improves quantification of PET/MR images in the pelvic region compared to the Dixon-based method.

Background: Cachexia and sarcopenia are associated with poor survival after colorectal cancer (CRC) diagnosis. Computed tomography (CT) can be used to measure aspects of cachexia including sarcopenia, myosteatosis and the amount of subcutaneous and visceral adipose tissue. The aim of this study was to relate CT-based body composition variables with survival outcomes in CRC. Material and methods: In this population-based, retrospective cohort study, CT scans of 974 patients with pathological stages I-IV CRCs, collected at or very near diagnosis (years 2000-2016), were used to measure cross-sectional fat and muscle tissue areas. Body composition variables based on these measurements were assessed in relation to tumor stage and site and cancer-specific survival in stages I-III CRC (n = 728) using Cox proportional hazards models and Kaplan-Meier estimators. Results: Sarcopenia was associated with decreased cancer-specific survival, especially in patients with stages I-II tumors. The hazard ratio (HR) for the lowest versus highest tertile of skeletal muscle index (SMI) was 1.67; 95% confidence interval (CI), 1.08-2.58 for all stages, and HR 2.22; 95% CI 1.06-4.68, for stages I-II. Myosteatosis was also associated with decreased cancer-specific survival [(HR 2.03; 95% CI 1.20-3.34 for the lowest versus the highest tertile of skeletal muscle radiodensity (SMR)]. SMI and SMR were lower in patients with right-sided CRC, independent of age and sex. No adipose tissue measurement was significantly associated with cancer-specific survival. Conclusion: In concordance with previous studies, sarcopenia and myosteatosis were associated with decreased cancer-specific survival. The strong association between sarcopenia and poor cancer-specific survival in early-stage disease could have clinical implications for personalizing therapy decisions, including nutritional support.

Purpose To enable the evaluation of locoregional disease in the on-going RECTOPET (REctal Cancer Trial on PET/MRI/CT) study; a methodology to match mesorectal imaging findings to histopathology is presented, along with initial observations. Methods FDG-PET/MRI examinations were performed in twenty-four consecutively included patients with rectal adenocarcinoma. In nine patients, of whom five received neoadjuvant treatment, a postoperative MRI of the surgical specimen was performed. The pathological cut-out was performed according to clinical routine with the addition of photo documentation of each slice of the surgical specimen, meticulously marking the location, size, and type of pathology of each mesorectal finding. This allowed matching individual nodal structures from preoperative MRI, via the specimen MRI, to histopathology. Results Preoperative MRI identified 197 mesorectal nodal structures, of which 92 (47%) could be anatomically matched to histopathology. Of the matched nodal structures identified in both MRI and histopathology, 25% were found to be malignant. These malignant structures consisted of lymph nodes (43%), tumour deposits (48%), and extramural venous invasion (9%). One hundred eleven nodal structures (55%) could not be matched anatomically. Of these, 97 (87%) were benign lymph nodes, and 14 (13%) were malignant nodal structures. Five were malignant lymph nodes, and nine were tumour deposits, all of which had a short axis diameter Conclusions We designed a method able to anatomically match and study the characteristics of individual mesorectal nodal structures, enabling further research on the impact of each imaging modality. Initial observations suggest that small malignant nodal structures assessed as lymph nodes in MRI often comprise other forms of mesorectal tumour spread. Trial registration Clinical Trials Identifier:NCT03846882.

We were encouraged to investigate the reasons for large amounts of foam observed in bloodlines during hemodialysis (HD). Foam was visible in the venous air trap within the Artis Gambro dialysis dev ...

The aim of this study was to evaluate the detection rate of bone metastases and the added value ofA total of 66 untreated patients with high-risk PC with ACE-PET/CT and planar BS findings within 3 months of each other were retrospectively enrolled. Findings were compared and verified with follow-up data after an average of 26 months.The rate of detection of bone metastases was superior with ACE-PET/CT compared to BS (p0.01). Agreement between the methods and between BS and follow-up was moderate (Cohen's kappa coefficient of 0.64 and 0.66, respectively). Agreement between ACE-PET/CT and follow-up was excellent (kappa coefficient of 0.95). Therapy was changed in 11% of patients due to ACE-PET/CT results.ACE-PET/CT performed better than planar BS in detection of bone metastases in high-risk PC. ACE-PET/CT findings influenced clinical management.

Purpose The role of hybrid imaging using 18F-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET), computed tomography (CT) and magnetic resonance imaging (MRI) to improve preoperative evaluation of rectal cancer is largely unknown. To investigate this, the RECTOPET (REctal Cancer Trial on PET/MRI/CT) study has been launched with the aim to assess staging and restaging of primary rectal cancer. This report presents the study workflow and the initial experiences of the impact of PET/CT on staging and management of the first patients included in the RECTOPET study. Methods This prospective cohort study, initiated in September 2016, is actively recruiting patients from Region Västerbotten in Sweden. This pilot study includes patients recruited and followed up until December 2017. All patients had a biopsy-verified rectal adenocarcinoma and underwent a minimum of one preoperative FDG-PET/CT and FDG-PET/MRI examination. These patients were referred to the colorectal cancer multidisciplinary team meeting at Umeå University Hospital. All available data were evaluated when making management recommendations. The clinical course was noted and changes consequent to PET imaging were described; surgical specimens underwent dedicated MRI for anatomical matching between imaging and histopathology. Results Twenty-four patients have so far been included in the study. Four patients were deemed unresectable, while 19 patients underwent or were scheduled for surgery; one patient was enrolled in a watch-and-wait programme after restaging. Consequent to taking part in the study, two patients were upstaged to M1 disease: one patient was diagnosed with a solitary hepatic metastasis detected using PET/CT and underwent metastasectomy prior to rectal cancer surgery, while one patient with a small, but metabolically active, lung nodulus experienced no change of management. PET/MRI did not contribute to any recorded change in patient management. Conclusions The RECTOPET study investigating the role of PET/CT and PET/MRI for preoperative staging of primary rectal cancer patients will provide novel data that clarify the value of adding hybrid to conventional imaging, and the role of PET/CT versus PET/MRI. Trial registration NCT03846882.

There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influence dopaminergic neurotransmission in the striatum, and in turn performance on offline working-memory updating tasks. Dopaminergic neurotransmission was measured by positron emission tomography (PET) and the non-displacable binding potential (BP

Background 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients. Methods Six low-risk prostate cancer patients were injected with 133–178 MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255 min post-injection. Urine was collected up to 4 h post-injection, and venous blood samples were drawn at 45 min, 85 min, 175 min, and 245 min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods. Results [68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5 min (91%) and 4.4 h (9%). The effective dose was calculated to 0.022 mSv/MBq. The kidneys received approximately 40 mGy after an injection with 160 MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12 mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051 mGy/MBq). Conclusion The effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.

Objective The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive. Methods The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study. Results Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance. Interpretation Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.

This is the Accepted Manuscript version of an article accepted for publication in Biomedical Engineering & Physics Express. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.1088/2057-1976/ab6496. Tracer kinetic modelling, based on dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used to quantify glucose metabolism in humans and animals. Knowledge of the arterial input-function (AIF) is required for such measurements. Our aim was to explore two non-invasive machine learning-based models, for AIF prediction in a small-animal dynamic FDG PET study. 7 tissue regions were delineated in images from 68 FDG PET/computed tomography mouse scans. Two machine learning-based models were trained for AIF prediction, based on Gaussian processes (GP) and a long short-term memory (LSTM) recurrent neural network, respectively. Because blood data were unavailable, a reference AIF was formed by fitting an established AIF model to vena cava and left ventricle image data. The predicted and reference AIFs were compared by the area under curve (AUC) and root mean square error (RMSE). Net-influx rate constants, Ki, were calculated with a two-tissue compartment model, using both predicted and reference AIFs for three tissue regions in each mouse scan, and compared by means of error, ratio, correlation coefficient, P value and Bland-Altman analysis. The impact of different tissue regions on AIF prediction was evaluated by training a GP and an LSTM model on subsets of tissue regions, and calculating the RMSE between the reference and the predicted AIF curve. Both models generated AIFs with AUCs similar to reference. The LSTM models resulted in lower AIF RMSE, compared to GP. Ki from both models agreed well with reference values, with no significant differences. Myocardium was highlighted as important for AIF prediction, but AIFs with similar RMSE were obtained also without myocardium in the input data. Machine learning can be used for accurate and non-invasive prediction of an image-derived reference AIF in FDG studies of mice. We recommend the LSTM approach, as this model predicts AIFs with lower errors, compared to GP.

Available online: 21 July 2018 Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity. Swedish Research Council [446-2013-7189] FORTE [2013-2277] Umea University Umea University-Karolinska Institute Strategic Neuroscience program Knut and Alice Wallenberg Foundation gs5:Torsten and Ragnar Soderberg Foundation Alexander von Humboldt Research award Swedish Brain Power Swedish Brain Foundation Vasterbotten County Council Max Planck Society German Research Foundation (DFG)

Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS). Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR). Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p

Introduction 11C-acetate (ACE)-PET/CT is used for staging of high-risk prostate cancer. PET data is reconstructed with iterative algorithms, such as VUEPointHD ViP (VPHD) and VUEPoint HD Sharp IR (SharpIR), the latter with additional resolution recovery. It is expected that the resolution recovery algorithm should render more accurate maximum and mean standardized uptake values (SUVmax and SUVmean) and functional tumor volumes (FTV) than the ordinary OSEM. Performing quantitative analysis, choice of volume-of-interest delineation algorithm (SUV threshold) may influence FTV. Optimizing PET acquisition time is justified if image quality and quantitation do not deteriorate. The aim of this study is to identify the optimal reconstruction algorithm, SUV threshold and acquisition time for ACE-PET/CT. Methods ACE-PET/CT data acquired with a General Electric Discovery 690 PET/CT from 16 consecutive high-risk prostate cancer patients was reconstructed with VPHD and SharpIR. Forty pelvic lymph nodes (LNs) and 14 prostate glands were delineated with 42% and estimated threshold. SUVmax, SUVmean, FTV and total lesion uptake were measured. Default acquisition time was four minutes per bed position. In a subset of lesions, acquisition times of one, two and four minutes were evaluated. Structural tumor volumes (STV) of the LNs were measured with CT for correlation with functional volumetric parameters. To validate SUV quantification under different conditions with SharpIR 42%, recovery coefficients (RCs) of SUVmean and FTV were calculated from a phantom with 18F-fluoro-deoxy-glucose (FDG)-filled volumes 0.1–9.2cm3 and signal-to-background (S/B) ratios 4.3–15.9. Results With SharpIR, SUVmax and SUVmean were higher and FTV lower compared with VPHD, regardless of threshold method, in both prostates and LNs. Total lesion uptake determined with both threshold methods was lower with SharpIR compared with VPHD with both threshold methods, except in subgroup analysis of prostate targets where estimated threshold returned higher values. Longer acquisition times returned higher FTV for both threshold methods, regardless of reconstruction algorithm. The FTV difference was most pronounced with one minute’s acquisition per bed position, which also produced visually the highest noise. SUV parameters were unaffected by varying acquisition times. FTV with SharpIR 42% showed the best correspondence with STV. SharpIR 42% gave higher RCs of SUVmean and FTV with increasing phantom size and S/B-ratio, as expected. Conclusions Delineation with SharpIR 42% seems to provide the most accurate combined information from SUVmax, SUVmean, FTV and total lesion uptake. Acquisition time may be shortened to two minutes per bed position with preserved image quality.

Purpose: Simultaneous collection of PET and MR data for radiotherapy purposes are useful for, for example, target definition and dose escalations. However, a prerequisite for using PET/MR in the radiotherapy workflow is the ability to image the patient in treatment position. The aim of this work was to adapt a GE SIGNA PET/MR scanner to image patients for radiotherapy treatment planning and evaluate the impact on signal-to-noise (SNR) of the MR images, and the accuracy of the PET attenuation correction. Method: A flat tabletop and a coil holder were developed to image patients in the treatment position, avoid patient contour deformation, and facilitate attenuation correction of flex coils. Attenuation corrections for the developed hardware and an anterior array flex coil were also measured and implemented to the PET/MR system to minimize PET quantitation errors. The reduction of SNR in the MR images due to the added distance between the coils and the patient was evaluated using a large homogenous saline-doped water phantom, and the activity quantitation errors in PET imaging were evaluated with and without the developed attenuation corrections. Result: We showed that the activity quantitation errors in PET imaging were within ±5% when correcting for attenuation of the flat tabletop, coil holder, and flex coil. The SNR of the MRI images were reduced to 74% using the tabletop, and 66% using the tabletop and coil holders. Conclusion: We present a tabletop and coil holder for an anterior array coil to be used with a GE SIGNA PET/MR scanner, for scanning patients in the radiotherapy work flow. Implementing attenuation correction of the added hardware from the radiotherapy setup leads to acceptable PET image quantitation. The drop in SNR in MR images may require adjustment of the imaging protocols.

Compartmental modeling of dynamic PET data enables quantification of tracer kinetics in vivo, through the calculated model parameters. In this study, we aimed to investigate the effect of early frame sampling and reconstruction method on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias and uncertainty (SD).The GATE Monte Carlo software was used to simulate 2 × 15 dynamic 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) brain PET studies, typical in terms of noise level and kinetic parameters. The data were reconstructed by both 3-dimensional (3D) filtered backprojection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6 dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15 s. Bias and SD were evaluated for fitted parameter estimates, calculated from regions of interest.The 2-tissue-model parameter estimates K1, k2, and fraction of arterial blood in tissue depended on early frame sampling, and a sampling of 6-15 s generally minimized bias and SD. The shortest sampling of 1 s yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM, respectively, and a parameter uncertainty that was 10%-70% higher. The schemes from 4 to 15 s were generally not significantly different in regards to bias and SD. Typically, the reconstruction method 3DRP yielded less frame-sampling dependence and less uncertain results, compared with OSEM, but was on average more biased.Of the 6 sampling schemes investigated in this study, an early frame duration of 6-15 s generally kept both bias and uncertainty to a minimum, for both 3DRP and OSEM reconstructions. Very-short frames of 1 s should be avoided because they typically resulted in the largest parameter bias and uncertainty. Furthermore, 3DRP may be preferred over OSEM for short frames with poor statistics.

The objective of this study was to compare the accuracy of calculating the primary tumor volumes using a gradient-based method and fixed threshold methods on the standardized uptake value (SUV) maps and the net influx of FDG (Ki) maps from positron emission tomography-computed tomography (PET-CT) images.Newly diagnosed patients with head and neck cancer were recruited, and dynamic PET-CT scan and T2-weighted magnetic resonance imaging were performed. The maps of Ki and SUV were calculated from PET-CT images. The tumor volumes were calculated using a gradient-based method and a fixed threshold method at 40% of maximal SUV or maximal Ki. Four kinds of volumes, VOLKi-Gra (from the Ki maps using the gradient-based method), VOLKi-40% (from the Ki maps using the threshold of 40% maximal Ki), VOLSUV-Gra (from the SUV maps using the gradient-based method), and VOLSUV-40% (from the SUV maps using the threshold of 40% maximal SUV), were acquired and compared with VOLMRI (the volumes acquired on T2-weighted images) using the Pearson correlation, paired t test, and similarity analysis.Eighteen patients were studied, of which 4 had poorly defined tumors (PDT). The positron emission tomography-derived volumes were as follows: VOLSUV-40%, 2.1 to 41.2 cm (mean [SD], 12.3 [10.6]); VOLSUV-Gra, 2.2 to 28.1 cm (mean [SD], 13.2 [8.4]); VOLKi-Gra, 2.4 to 17.0 cm (mean [SD], 9.5 [4.6]); and VOLKi-40%, 2.7 to 20.3 cm (mean [SD], 12.0 [6.0]). The VOLMRI ranged from 2.9 to 18.1 cm (mean [SD], 9.1 [3.9]). The VOLKi-Gra significantly correlated with VOLMRI with the highest correlation coefficient (PDT included, R = 0.673, P = 0.002; PDT excluded, R = 0.841, P0.001) and presented no difference from VOLMRI (P = 0.672 or 0.561, respectively, PDT included and excluded). The difference between VOLKi-Gra and VOLMRI was also the smallest.The tumor volumes delineated on the Ki maps using the gradient-based method are more accurate than those on the SUV maps and using the fixed threshold methods.

Attenuation correction is a requirement for quantification of the activity distribution in PET. The need to base attenuation correction on MRI instead of CT has arisen with the introduction of integrated PET/MRI systems. The aim was to describe the effect of residual gradient field nonlinearity distortions on PET attenuation correction.MRI distortions caused by gradient field nonlinearity were simulated in CT images used for attenuation correction in PET reconstructions. The simulations yielded radial distortion of up to ±2.3mm at 15cm from the scanner isocentre for distortion corrected images. The mean radial distortion of uncorrected images were 6.3mm at the same distance. Reconstructions of PET data were performed using the distortion corrected images as well as the images where no correction had been applied.The mean relative difference in reconstructed PET uptake intensity due to incomplete distortion correction was less than ±5%. The magnitude of this difference varied between patients and the size of the distortions remaining after distortion correction.Radial distortions of 2mm at 15cm radius from the scanner isocentre lead to PET attenuation correction errors smaller than 5%. Keeping the gradient field nonlinearity distortions below this limit can be a reasonable goal for MRI systems used for attenuation correction in PET for quantification purposes. A higher geometrical accuracy may, however, be warranted for quantification of peripheral lesions. These distortions can, e.g., be controlled at acceptance testing and subsequent quality assurance intervals.

Early and persisting response to vismodegib in a patient with bone metastasizing medulloblastoma

The aim of this study was to evaluate MR-based attenuation correction of PET emission data of the head, based on a previously described technique that calculates substitute CT (sCT) images from a set of MR images.Images from eight patients, examined with (18)F-FLT PET/CT and MRI, were included. sCT images were calculated and co-registered to the corresponding CT images, and transferred to the PET/CT scanner for reconstruction. The new reconstructions were then compared with the originals. The effect of replacing bone with soft tissue in the sCT-images was also evaluated.The average relative difference between the sCT-corrected PET images and the CT-corrected PET images was 1.6% for the head and 1.9% for the brain. The average standard deviations of the relative differences within the head were relatively high, at 13.2%, primarily because of large differences in the nasal septa region. For the brain, the average standard deviation was lower, 4.1%. The global average difference in the head when replacing bone with soft tissue was 11%.The method presented here has a high rate of accuracy, but high-precision quantitative imaging of the nasal septa region is not possible at the moment.

Most of the methods used for analyzing PET data are applied in the spatial domain (image domain), in which reconstructed images contain all different types of effects and errors caused by the reconstruction algorithm such as correlation in-between pixels, correlations in-between frames, and streak-artifacts. In this paper, we have investigated a new, pixel wise, noise prenormalization method used for transformation of input data followed by volume-wise application of principal component analysis (PCA) on masked dynamic PET data in the sinogram domain. We are aiming to improve the performance of PCA and to provide images with improved quality and signal extraction. We compare the performance of PCA and the image quality obtained with the new method with previously published approaches. The results show improvement of performance of PCA with respect to image quality, signal extraction, precision, and visualization

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Background: Radiation treatment with simultaneous integrated boost against suspected lymph node metastases may be a curative therapeutic option in patients with high-risk prostate cancer (>15% estimated risk of pelvic lymph node metastases according to the Cagiannos nomogram). 11C-acetate positron emission tomography/computed tomography (PET/CT) can be used for primary staging as well as for detection of suspected relapse of prostate cancer. The aims of this study were to evaluate the association between positive 11C-acetate PET/CT findings and the estimated risk of pelvic lymph node metastases and to assess the impact of 11C-acetate PET/CT on patient management in high-risk prostate cancer patients. Methods: Fifty consecutive prostate cancer patients referred for primary staging with 11C-acetate PET/CT prior to radiotherapy with curative intention were enrolled in this retrospective study. Results: All patients showed increased 11C-acetate uptake in the prostate. Pelvic lymph node uptake was seen in 42% (21/50) of the patients, with positive external iliac lymph nodes in 71% (15/21) of these. The overall observed proportion of PET/CT-positive pelvic lymph nodes at patient level was higher than the average estimated risk, especially in low-risk groups (45% estimated risk. Treatment strategy was altered due to 11C-acetate PET/CT findings in 43% (20/47) of the patients. Conclusions: The observed proportion of 11C-acetate PET/CT findings suggestive of locoregional metastases was higher than the estimated risk, suggesting that the Cagiannos nomogram underestimates the risk for metastases. The imaging results with 11C-acetate PET/CT have a considerable impact on patient management.

What effects will the implementation of the quality standard ISO 9000 have regarding working conditions and competitive advantages? Which are the most important change process characteristics for assuring improved working conditions and other desired effects? These are the main questions behind this study of six furniture-making companies which implemented ISO 9000 during the period 1991-1994. The results show that customer requirement was the dominant goal to implement ISO 9000. Five of the six companies succeeded in gaining certification. The influence on working conditions was limited, but included better order and housekeeping, more positive attitudes towards discussing quality shortcomings, a few workplace improvements, work enrichment caused by additional tasks within the quality system and a better understanding of external customer demands. Among the negative effects were new, apparently meaningless, tasks for individual workers as well as more stress and more physically strenuous work. The effects on the companies included a decrease in external quality-related costs and improved delivery precision. The study confirms the importance for efficient change of the design of the change process, and identifies 'improvement methodology' as the most important process characteristic. Improved working conditions are enhanced by added relevant strategic goals and by a participative implementation process.

In PET, partial-volume effects cause errors in estimation of size and activity for small objects with radiopharmaceutical uptake. Recent methods for image reconstruction, compared with traditional reconstruction techniques, include algorithms for resolution recovery that result in images with higher resolution and enable quantification of size and activity of smaller objects. The purpose of this study was to evaluate a combination of 2 algorithms for volume delineation and partial-volume correction on uptake volumes smaller than 0.7 mL using image reconstruction algorithms with and without resolution recovery.Volumes of interests (VOIs) were delineated using a threshold intensity calculated as a weighted sum of tumor and background intensities. These VOIs were used for calculating correction factors by convolving a tumor mask with the system point-spread function. The methods algorithms were evaluated using a phantom constructed from 5 small different-sized balloons filled with (18)F-FDG in background activity. Six different backgrounds were used. Data were acquired using a PET/CT scanner, and the images were reconstructed using 2 iterative algorithms, one of which used a resolution recovery algorithm.For the images reconstructed using the resolution recovery algorithm, the method for volume delineation resulted in VOI sizes that were correct within 1 SD for all balloons of a volume of 0.35 mL (equivalent diameter, 8.8 mm) and larger, in all backgrounds. For the images reconstructed without resolution recovery, the VOI sizes were background-dependent and generally less accurate. Correct volume delineations generally led to accurate activity estimates.The algorithms tested on the phantom developed for this study could, for this PET camera and these reconstruction algorithms, be used for accurate volume delineation and activity quantification of lesions 0.35 mL and larger.

Background In this paper we apply the principal-component analysis filter (Hotelling filter) to reduce noise from dynamic positron-emission tomography (PET) patient data, for a number of different radio-tracer molecules. We furthermore show how preprocessing images with this filter improves parametric images created from such dynamic sequence. We use zero-mean unit variance normalization, prior to performing a Hotelling filter on the slices of a dynamic time-series. The Scree-plot technique was used to determine which principal components to be rejected in the filter process. This filter was applied to [11C]-acetate on heart and head-neck tumors, [18F]-FDG on liver tumors and brain, and [11C]-Raclopride on brain. Simulations of blood and tissue regions with noise properties matched to real PET data, was used to analyze how quantitation and resolution is affected by the Hotelling filter. Summing varying parts of a 90-frame [18F]-FDG brain scan, we created 9-frame dynamic scans with image statistics comparable to 20 MBq, 60 MBq and 200 MBq injected activity. Hotelling filter performed on slices (2D) and on volumes (3D) were compared. Results The 2D Hotelling filter reduces noise in the tissue uptake drastically, so that it becomes simple to manually pick out regions-of-interest from noisy data. 2D Hotelling filter introduces less bias than 3D Hotelling filter in focal Raclopride uptake. Simulations show that the Hotelling filter is sensitive to typical blood peak in PET prior to tissue uptake have commenced, introducing a negative bias in early tissue uptake. Quantitation on real dynamic data is reliable. Two examples clearly show that pre-filtering the dynamic sequence with the Hotelling filter prior to Patlak-slope calculations gives clearly improved parametric image quality. We also show that a dramatic dose reduction can be achieved for Patlak slope images without changing image quality or quantitation. Conclusions The 2D Hotelling-filtering of dynamic PET data is a computer-efficient method that gives visually improved differentiation of different tissues, which we have observed improve manual or automated region-of-interest delineation of dynamic data. Parametric Patlak images on Hotelling-filtered data display improved clarity, compared to non-filtered Patlak slope images without measurable loss of quantitation, and allow a dramatic decrease in patient injected dose.

UNLABELLED: Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-(11)C]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole ((11)C-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of (11)C-PIB PET in systemic amyloidosis affecting the heart.METHODS: Patients (n = 10) diagnosed with systemic amyloidosis-including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type-and healthy volunteers (n = 5) were investigated with PET/CT using (11)C-PIB to study cardiac amyloid deposits and with (11)C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention.RESULTS: Myocardial (11)C-PIB uptake was visually evident in all patients 15-25 min after injection and was not seen in any volunteer. A significant difference in (11)C-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with (11)C-PIB. No correlation between (11)C-PIB retention index and myocardial blood flow as measured with (11)C-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient.CONCLUSION: (11)C-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.

In In-111- pentetreotide single-photon emission computed tomography (SPECT), the tumor-to-background-uptake ratio is generally high. The noise is, however, also usually on a high level, and in combination with the low spatial resolution of SPECT, this may lead to difficulties in the detection of small tumors. This is especially the case in regions with a relatively high background activity, such as in the liver, which is a common region for somatostatin-positive metastases. Visually detecting the small tumors is important for a successful treatment of the cancer disease. In this paper, we compare three different parallel-hole collimators for In-111-pentetreotide SPECT regarding contrast as a function of image noise for a phantom simulating small tumors in liver background. The corresponding contrast-to-noise ratios are also presented. All raw-data projections are produced using Monte Carlo simulations. The collimators are of type low-energy general-purpose (LEGP), extended LEGP (ELEGP), and medium-energy general-purpose (MEGP). Reconstructions were performed with OSEM both with and without model-based compensation. Of the investigated collimators, the ELEGP collimator proved to be the most optimal for the smallest tumors, both with and without model-based compensation included in the reconstruction. It is also shown that model-based compensation outperforms the conventional reconstruction technique.

Principal component analysis (PCA) is one of the most applied multivariate image analysis tool on dynamic Positron Emission Tomography (PET). Independent of used reconstruction methodologies, PET images contain correlation in-between pixels, correlations in-between frame and errors caused by the reconstruction algorithm including different corrections, which can affect the performance of the PCA. In this study, we have investigated a new approach of application of PCA on pre-normalized, dynamic human PET images. A range of different tracers have been used for this purpose to explore the performance of the new method as a way to improve detection and visualization of significant changes in tracer kinetics and to enhance the discrimination between pathological and healthy regions in the brain. We compare the new results with the results obtained using other methods. Images generated using the new approach contain more detailed anatomical information with higher quality, precision and visualization, compared with images generated using other methods.

A polymer microchip with an open tip for electrospray mass spectrometry is presented. The tip consists of a groove with parallel walls where a droplet can form at the end surface. A lid covers the whole chip except at the microchannel tip, which is left open. Poly(dimethylsiloxane) (PDMS) microchips were cast using a nickel mould which in turn was replicated from a dry etched silicon wafer. Tips with microchannel widths of around 50 microm could easily be replicated. Since the tip had no cover, the assembly of microchip and cover was simplified. A total ion current variation of 5% during 300 s was achieved for a 1 microM myoglobin solution. The non-complex design of the cover makes it suitable for versatile tests of chip prototypes. The nickel mould was found to be useful for PDMS microstructure fabrication. Also, such a robust mould allows casting electrospray tips in more rigid thermoset materials.

Thirty-nine cases of male breast cancer were reported to the Swedish Cancer Registry in 1962–1963, and sufficient information was gained from 34 of them for inclusion in this study. Male breast cancer constitutes 0.7% of the total number of breast cancers. The average age at time of diagnosis was 65 years. Many of the patients had complicating diseases. The patient's delay in seeking medical attention was an average of 7.9 months. Fifty-nine percent of the tumors were situated in the left breast. Four patients (12%) had gynecomastia. Fifteen percent of the cancers were clinical stage I, 38% stage II, 35% stage III, and 12% stage IV at the time of diagnosis. Twenty-one percent had histologically proven nodal metastases. Twenty-seven patients underwent a more or less radical operation. Most patients received radiotherapy after operative treatment. The overall corrected 5-year survival is 54% and 10-year survival 37%. A review of the literature is given.

Thirty-nine cases of male breast cancer were reported to the Swedish Cancer Registry in 1962–1963, and sufficient information was gained from 34 of them for inclusion in this study. Male breast cancer constitutes 0.7% of the total number of breast cancers. The average age at time of diagnosis was 65 years. Many of the patients had complicating diseases. The patient's delay in seeking medical attention was an average of 7.9 months. Fifty-nine percent of the tumors were situated in the left breast. Four patients (12%) had gynecomastia. Fifteen percent of the cancers were clinical stage I, 38% stage II, 35% stage III, and 12% stage IV at the time of diagnosis. Twenty-one percent had histologically proven nodal metastases. Twenty-seven patients underwent a more or less radical operation. Most patients received radiotherapy after operative treatment. The overall corrected 5-year survival is 54% and 10-year survival 37%. A review of the literature is given.