Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation.

We report the results of a Phase I radiation dose escalation study using an yttrium-90 (90Y) labelled anti-CD66 monoclonal antibody given with standard conditioning regimen for patients receiving haematopoietic stem cell transplants for myeloid leukaemia or myeloma. The 90Y-labelled anti-CD66 was infused prior to standard conditioning. In total, 30 patients entered the trial and 29 received 90Y-labelled mAb, at infused radiation activity levels of 5, 10, 25, or 37.5 megaBequerel (MBq)/kg lean body weight. A prerequisite for receiving the 90Y-labelled mAb was favourable dosimetry determined by single-photon emission computerised tomography (SPECT) dosimetry following administration of indium-111 (111In) anti-CD66. Estimated absorbed radiation doses delivered to the red marrow demonstrated a linear relationship with the infused activity of 90Y-labelled mAb. At the highest activity level of 37.5 MBq/kg, mean estimated radiation doses for red marrow, liver, spleen, kidneys and lungs were 24.6 ± 5.6 Gy, 5.8 ± 2.7 Gy, 19.1 ± 8.0 Gy, 2.1 ± 1.1 and 2.2 ± 0.9, respectively. All patients engrafted, treatment-related mortality 1-year post-transplant was zero. Toxicities were no greater than those anticipated for similar conditioning regimens without targeted radiation. The ability to substantially intensify conditioning prior to haematopoietic stem cell transplantation without increasing toxicity warrants further testing to determine efficacy. clinicaltrials.gov identifier: NCT01521611.

ADCOMS sensitivity versus baseline diagnosis and progression phenotypes.

BACKGROUND: The Alzheimer's Disease COMposite Score (ADCOMS) is more sensitive in clinical trials than conventional measures when assessing pre-dementia. This study compares ADCOMS trajectories using clustered progression characteristics to better understand different patterns of decline. METHODS: Post-baseline ADCOMS values were analyzed for sensitivity using mean-to-standard deviation ratio (MSDR), partitioned by baseline diagnosis, comparing with the original scales upon which ADCOMS is based. Because baseline diagnosis was not a particularly reliable predictor of progression, individuals were also grouped into similar ADCOMS progression trajectories using clustering methods and the MSDR compared for each progression group. RESULTS: ADCOMS demonstrated increased sensitivity for clinically important progression groups. ADCOMS did not show statistically significant sensitivity or clinical relevance for the less-severe baseline diagnoses and marginal progression groups. CONCLUSIONS: This analysis complements and extends previous work validating the sensitivity of ADCOMS. The large data set permitted evaluation-in a novel approach-by the clustered progression group.

Perfusion Imaging and Inflammation Biomarkers Provide Complementary Information in Alzheimer's Disease.

BACKGROUND: Single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis. OBJECTIVE: In this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer's disease (AD). METHODS: We analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD. RESULTS: Regional perfusion reduction in the precuneus and medial temporal regions predicted Aß42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85. CONCLUSIONS: Study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction.

Artificial intelligence for diagnostic and prognostic neuroimaging in dementia: A systematic review.

INTRODUCTION: Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia. METHODS: We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases. RESULTS: A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort. DISCUSSION: The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice. HIGHLIGHTS: There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other individual dataset used more than five times There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls We make recommendations to address methodological considerations, addressing key clinical questions, and validation We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias.

Brain PET and SPECT imaging and quantification: a survey of the current status in the UK.

OBJECTIVES: With disease-modifying therapies in development for neurological disorders, quantitative brain imaging techniques become increasingly relevant for objective early diagnosis and assessment of response to treatment. The aim of this study was to evaluate the use of Brain SPECT and PET scans in the UK and explore drivers and barriers to using quantitative analysis through an online survey. METHODS: A web-based survey with 27 questions was used to capture a snapshot of brain imaging in the UK. The survey included multiple-choice questions assessing the availability and use of quantification for DaTscan, Perfusion SPECT, FDG PET and Amyloid PET. The survey results were reviewed and interpreted by a panel of imaging experts. RESULTS: Forty-six unique responses were collected and analysed, with 84% of responses from brain imaging sites. Within these sites, 88% perform DaTscan, 50% Perfusion SPECT, 48% FDG PET, and 33% Amyloid PET, while a few sites use other PET tracers. Quantitative Brain analysis is used in 86% of sites performing DaTscans, 40% for Perfusion SPECT, 63% for FDG PET and 42% for Amyloid PET. Commercial tools are used more frequently than in-house software. CONCLUSION: The survey showed variations across the UK, with high availability of DaTscan imaging and quantification and lower availability of other SPECT and PET scans. The main drivers for quantification were improved reporting confidence and diagnostic accuracy, while the main barriers were a perception of a need for an appropriate database of healthy controls and a lack of training, time, and software availability.

Biomarkers of Inflammation Increase with Tau and Neurodegeneration but not with Amyloid-ß in a Heterogenous Clinical Cohort.

BACKGROUND: Neuroinflammation is an integral part of Alzheimer's disease (AD) pathology. Inflammatory mediators can exacerbate the production of amyloid-ß (Aß), the propagation of tau pathology and neuronal loss. OBJECTIVE: To evaluate the relationship between inflammation markers and established markers of AD in a mixed memory clinic cohort. METHODS: 105 cerebrospinal fluid (CSF) samples from a clinical cohort under investigation for cognitive complaints were analyzed. Levels of Aß42, total tau, and phosphorylated tau were measured as part of the clinical pathway. Analysis of inflammation markers in CSF samples was performed using multiplex immune assays. Participants were grouped according to their Aß, tau, and neurodegeneration status and the Paris-Lille-Montpellier (PLM) scale was used to assess the likelihood of AD. RESULTS: From 102 inflammatory markers analyzed, 19 and 23 markers were significantly associated with CSF total tau and phosphorylated tau levels respectively (p < 0.001), while none were associated with Aß42. The CSF concentrations of 4 inflammation markers were markedly elevated with increasing PLM class indicating increased likelihood of AD (p < 0.001). Adenosine deaminase, an enzyme involved in sleep homeostasis, was the single best predictor of high likelihood of AD (AUROC 0.788). Functional pathway analysis demonstrated a widespread role for inflammation in neurodegeneration, with certain pathways explaining over 30% of the variability in tau values. CONCLUSION: CSF inflammation markers increase significantly with tau and neurodegeneration, but not with Aß in this mixed memory clinic cohort. Thus, such markers could become useful for the clinical diagnosis of neurodegenerative disorders alongside the established Aß and tau measures.

A comparison of thyroid blockade strategies in paediatric 123I-meta-iodobenzylguanidine scanning: a dual centre study.

OBJECTIVE: The aim of this study was to evaluate three thyroid blockade regimes to determine which protocol provides the optimal level of thyroidal protection for paediatric 123-I-meta-iodobenzylguanidine (mIBG) imaging and estimate the relative radiation dose inferred from unbound radioiodine. METHODS: A total of 231 patients were retrospectively evaluated for thyroid uptake and categorised into five subgroups depending upon the protocol of thyroid blockade received. Efficacy of thyroid blockade was established by visual scoring and image quantitation with comparison against a control group. RESULTS: Visual Likert scale responses were subjected to the Mann-Whitney U and Kruskal-Wallis tests, respectively. Statistical significance was reached for observed thyroid uptake in potassium perchlorate recipients (U = 1107, P = 0.001). No statistically significant difference was observed in thyroid uptake for iohexol blockade (U = 176, P = 0.71) or potassium iodate blockade despite variations in iodate dosage and duration (χ(2) = 0.203, P = 0.93). The analyses were repeated for the image quantitation data. A statistically significantly higher absorbed thyroid dose was observed using potassium perchlorate blockade compared with the control group (U = 719, P = 0.001). The Mann-Whitney U did not reach statistical significance in absorbed thyroid dose for iohexol blockade (U = 126, P = 0.209, r = -0.13). The Kruskal-Wallis test, conducted across the potassium iodate groups, did not reach statistical significance (χ(2) = 0.513, P = 0.774). The median absorbed thyroid dose across the iodate groups ranged from 3.58 to 3.91 mGy indicating comparable blockade effectiveness for single-dose potassium iodate. CONCLUSION: Potassium iodate blockade is more efficacious compared with potassium perchlorate within the cohort observed. Both visual and quantitative data indicate that potassium iodate given at 30-60 min before I-mIBG injection provides comparable blockade effectiveness to lengthier administrations, suggesting that a single dose is well tolerated and practical.

Standardised quantitative radioiodine SPECT/CT Imaging for multicentre dosimetry trials in molecular radiotherapy.

The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose-response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8-196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient's activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities' were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.

Discovery Molecular Imaging Digital Ready PET/CT performance evaluation according to the NEMA NU2-2012 standard.

OBJECTIVES: The aim of this study was to evaluate and benchmark the performance characteristics of the General Electric (GE) Discovery Molecular Imaging (MI) Digital Ready (DR) PET/CT. MATERIALS AND METHODS: Performance evaluation against the National Electrical Manufacturers Association (NEMA) 2012 standard was performed on three GE Discovery MI DR PET/CT systems installed across different UK centres. The Discovery MI DR performance was compared with the Siemens Biograph mCT Flow, Phillips Ingenuity TF and GE Discovery 690 fully analogue PET/CT systems. In addition, as the Discovery MI DR is upgradable to the Digital MI with silicon photomultipliers, performance characteristics between analogue and digital were compared with assess potential benefits of a system upgrade. RESULTS: The average NEMA results across three Discovery MI DR scanners were: sensitivity 7.3 cps/kBq, spatial resolution full-width-half-maximum radial 5.5 mm, tangential 4.5 mm and axial 6 mm at 10 cm from the centre of the field-of-view, peak noise equivalent count rate 142 kcps, scatter fraction 37.1%, contrast recovery coefficients from the International Electrotechnical Commission phantom ranged from 52 to 87% for 10-37-mm diameter spheres. CONCLUSION: All three Discovery MI DR systems tested in this study exceeded the manufacturer's NEMA specification, yet variability between scanners was noted. Discovery MI DR showed similar performance to Discovery 690 and Ingenuity TF, but lower sensitivity and spatial resolution than Biograph mCT Flow. The Discovery MI DR showed lower spatial resolution and contrast recovery than the 20-cm field-of-view Digital MI.

Investigating the role of SPECT/CT in dynamic sentinel lymph node biopsy for penile cancers.

PURPOSE: Currently, most centres use 2-D planar lymphoscintigraphy when performing dynamic sentinel lymph node biopsy in penile cancer patients with clinically impalpable inguinal nodes. This study aimed to investigate the role of SPECT/CT following 2-D planar lymphoscintigraphy (dynamic and static) in the detection and localization of sentinel lymph nodes in the groin. METHODS: A qualitative (visual) review was performed on planar followed by SPECT/CT lymphoscintigraphy in 115 consecutive patients (age 28-86 years) who underwent injection of 99mTc-nanocolloid followed by immediate acquisition of dynamic (20 min) and early static scans (5 min) initially and further delayed static (5 min) images at 120 min followed by SPECT/CT imaging. The lymph nodes detected in each groin on planar lymphoscintigraphy and SPECT/CT were compared. RESULTS: A total of 440 and 467 nodes were identified on planar scintigraphy and SPECT/CT, respectively. Overall, SPECT/CT confirmed the findings of planar imaging in 28/115 cases (24%). In the remaining 87 cases (76%), gross discrepancies were observed between planar and SPECT/CT images. SPECT/CT identified 17 instances of skin contamination (16 patients, 13%) and 36 instances of in-transit lymphatic tract activity (24 patients, 20%) that had been interpreted as tracer-avid lymph nodes on planar imaging. In addition, SPECT/CT identified 53 tracer-avid nodes in 48 patients (42%) that were not visualized on planar imaging and led to reclassification of the drainage basins (pelvic/inguinal) of 27 tracer-avid nodes. CONCLUSIONS: The addition of SPECT/CT improved the rate of detection of true tracer-avid lymph nodes and delineated their precise (3-D) anatomic localization in drainage basins.

PET/CT Imaging of Unstable Carotid Plaque with 68Ga-Labeled Somatostatin Receptor Ligand.

68Ga-labeled somatostatin receptor ligand PET imaging has recently been shown in preclinical and early human studies to have a potential role in the evaluation of vulnerable arterial plaques. We prospectively evaluated carotid plaque 68Ga-DOTATATE uptake in patients with recent carotid events, assessed inter- and intraobserver variability of such measurements, and explored the mechanism of any plaque DOTATATE activity with immunohistochemistry in resected specimens. Methods: Twenty consecutively consenting patients with recent symptomatic carotid events (transient ischemic attack, stroke, or amaurosis fugax), due for carotid endarterectomy, were prospectively recruited. 68Ga-DOTATATE PET/CT of the neck was performed before surgery. 68Ga-DOTATATE uptake was measured by drawing regions of interest along the carotid plaques and contralateral plaques/carotid arteries by an experienced radionuclide radiologist and radiographer. Two PET quantification methods with inter- and intraobserver variability were assessed. Resected carotid plaques were retrieved for somatostatin receptor subtype-2 (sst2) immunohistochemical staining. Results: The median time delay between research PET and surgery was 2 d. SUVs and target-to-background ratios for the symptomatic plaques and the asymptomatic contralateral carotid arteries/plaques showed no significant difference (n = 19, P > 0.10), regardless of quantification method. The intraclass correlation coefficient was greater than 0.8 in all measures of carotid artery/plaque uptake (SUV) and greater than 0.6 in almost all measures of target-to-background ratio. None of the excised plaques was shown to contain cells (macrophages, lymphocytes, vessel-associated cells) expressing sst2 on their cell membrane. Conclusion:68Ga-DOTATATE activity on PET in recently symptomatic carotid plaques is not significantly different from contralateral carotids/plaques. Any activity seen on PET is not shown to be from specific sst2 receptor-mediated uptake in vitro. It is therefore unlikely that sst2 PET/CT imaging will have a role in the detection and characterization of symptomatic carotid plaques.

Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors.

This study aimed to assess the clinical impact of 68Ga-DOTATATE and 18F-FDG with respect to the management plan and to evaluate the prognostic value of both tracers. METHODS: A total of 104 patients (55 male and 49 female; median age, 58 y; range, 20-90 y) with histologically proven neuroendocrine tumors (NETs) underwent both 68Ga-DOTATATE and 18F-FDG PET/CT. Twenty-eight patients (26.9%) had poorly differentiated tumors, and 76 (73.1%) had well-differentiated tumors. PET/CT results and SUVs were compared with prognostic factors such as histologic grade (G1, G2, or G3, for low-grade [well differentiated], intermediate-grade [moderately differentiated], and high-grade [poorly differentiated], respectively), chromogranin A, and proliferation index (Ki-67). RESULTS: The 68Ga-DOTATATE and 18F-FDG PET/CT findings were discordant in 65 patients (62.5%) and concordant in 39 patients (37.5%). The results changed the therapeutic plan in 84 patients (80.8%). In 22 patients (21.1%), decision making was based on the 18F-FDG findings; in 32 (30.8%), on the findings with both radiotracers; and in 50 (48.1%), on the 68Ga-DOTATATE findings. The most frequent management decision based on 18F-FDG was initiation of chemotherapy (10 patients, 47.6%). The most common treatment decision due to 68Ga-DOTATATE was initiation of peptide receptor radionuclide therapy (14 patients, 27.4%). In 11 (39.2%) of 28 patients with poorly differentiated NETs, the management decision was based on only the 18F-FDG results. For 68Ga-DOTATATE, SUVmax was higher for G1 tumors and lower for G3 tumors (P = 0.012). However, no significant differences in 18F-FDG-derived SUVs were observed between different grades (P = 0.38). The Mann-Whitney test showed significant differences in 68Ga-DOTATATE SUVmax between tumors with a Ki-67 of less than 5% and tumors with a Ki-67 of more than 5% (P = 0.004), without significance differences in 18F-FDG SUVmax Log-rank analysis showed statistically significant differences in survival for patients with bone metastasis versus soft-tissue or no metastasis for both 18F-FDG (P = 0.037) and 68Ga-DOTATATE (P = 0.047). Overall survival declined rapidly with increasing grade (P = 0.001), at an estimated 91 mo for G1, 59 mo for G2, and 48 mo for G3. CONCLUSION: 18F-FDG PET/CT had no clinical impact on G1 NETs and a moderate impact on G2 NETs. However, in poorly differentiated NETs, 18F-FDG PET/CT plays a significant clinical role in combination with 68Ga-DOTATATE. 68Ga DOTATATE SUVmax relates to grade and Ki-67 and can be used prognostically.

The Impact of 68Ga-DOTATATE PET/CT Imaging on Management of Patients with Neuroendocrine Tumors: Experience from a National Referral Center in the United Kingdom.

UNLABELLED: (68)Ga-DOTATATE PET/CT scanning is a widely accepted method for imaging of neuroendocrine tumors. This cross-sectional study was performed to review the first 8 y of patient data from a large (68)Ga-DOTATATE PET/CT database in order to establish the impact of the modality on patient treatment and survival. METHODS: Demographic data, clinical outcome, survival, and change in management after (68)Ga-DOTATATE PET/CT were evaluated. RESULTS: Between May 2005 and August 2013, 1,258 (68)Ga-DOTATATE PET/CT scans were obtained in 728 patients with confirmed or suspected neuroendocrine tumors. In most patients, the primary site was located in the midgut (26.4%). Analysis of NET grading in patients with known histopathologic data revealed that 35.7% had NET grade G1, 12.2% G2, and 8.7% G3. The most common indications for (68)Ga-DOTATATE PET/CT were follow-up (24.4%) and initial tumor staging (23.4%). Of the 1,258 (68)Ga-DOTATATE PET/CT scans completed, 75.7% were positive and 24.3% negative; there were 14 false-positive and 29 false-negative scans. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 97%, 95.1%, 96.6%, 98.5%, and 90.4%, respectively. In 40.9% of patients, the treatment plan was changed after the scans, owing mainly to new, unexpected findings. Statistically significant differences in survival were shown between patients with G1, G2, and G3 grade tumors (P < 0.0001) and also between patients with bone metastasis versus patients with soft-tissue metastasis (P < 0.0001). CONCLUSION: (68)Ga-DOTATATE PET/CT scanning is safe and influences management in a large proportion of patients. Prognosis was dependent on tumor grade, and the presence of bone metastasis was associated with worse overall survival.

Pitfalls and artifacts using the D-SPECT dedicated cardiac camera.

Myocardial perfusion imaging is a well-established and widely used imaging technique for the assessment of patients with known or suspected coronary artery disease. Pitfalls and artifacts associated with conventional gamma cameras are well known, and the ways to avoid and correct them have been described. In recent years solid-state detector dedicated cardiac cameras were introduced and have been shown to offer improved accuracy in addition to new imaging protocols and novel applications. The purpose of this manuscript is to familiarize the readers with the causes and effects of technical, patient-related, and operator-related pitfalls and artifacts associated with the D-SPECT dedicated cardiac camera with solid-state detectors. The manuscript offers guidance on how to avoid these factors, how to detect them, and how to correct better for them, providing high-quality diagnostic images.

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series.

BACKGROUND: Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. OBJECTIVES: The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. METHOD: PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen's kappa. RESULTS: Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0-0.25 for PCA to 0.29-0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. CONCLUSION: The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice.

18F-fluoroethylcholine (18F-Cho) PET/MRI functional parameters in pediatric astrocytic brain tumors.

PURPOSE: To examine the feasibility of simultaneous acquisition of F-fluoroethylcholine (F-choline) PET and functional MRI (standardized uptake value [SUV]max/mean and apparent diffusion coefficient [ADC]mean), using a hybrid PET/MRI scanner, for diagnosis and response assessment in a cohort of children with astrocytic brain tumors. METHODS: F-choline PET/MRI scans were performed in 12 patients with proven astrocytic tumors.Eight patients simultaneously underwent F-choline PET/MR follow-up scans after treatment. Uptake in the lesion above the normal brain activity was considered indicative of a positive scan. Maximum and mean SUVs (SUVmax and SUVmean) and mean ADC (ADCmean) of the whole tumor region of interest were assessed. Lesion size and contrast enhancement were recorded. For all tumors, the association between ADCmean and SUVmean/SUVmax values were assessed using the Spearman correlation coefficient. RESULTS: At baseline, the areas of F-choline uptake matched areas of contrast enhancement and restricted diffusion. There was a negative correlation trend between SUVmax and ADCmean and a positive correlation trend between SUVmax and tumor size. There was concordance between reduction in tumor size and reductions in SUVmax and SUVmean in 4 children, in three of whom ADCmean values were increased. In 2 patients, tumor size remained stable whereas SUVmax and SUVmean values were increased with reduction in the ADCmean values. Additionally, in 2 children, cross-sectional MRI showed an increase both in tumor size and SUVmax but a reduction in ADC values. CONCLUSIONS: Simultaneous F-choline PET/MRI is a promising and reliable imaging tool for children with astrocytic tumors, as it permits monitoring of morphological and metabolic response and changes during therapy.

Qualitative and quantitative comparison of PET/CT and PET/MR imaging in clinical practice.

UNLABELLED: The aim of this study was to prospectively compare whole-body PET/MR imaging and PET/CT, qualitatively and quantitatively, in oncologic patients and assess the confidence and degree of inter- and intraobserver agreement in anatomic lesion localization. METHODS: Fifty patients referred for staging with known cancers underwent PET/CT with low-dose CT for attenuation correction immediately followed by PET/MR imaging with 2-point Dixon attenuation correction. PET/CT scans were obtained according to standard protocols (56 ± 20 min after injection of an average 367 MBq of (18)F-FDG, 150 MBq of (68)Ga-DOTATATE, or 333.8 MBq of (18)F-fluoro-ethyl-choline; 2.5 min/bed position). PET/MR was performed with 5 min/bed position. Three dual-accredited nuclear medicine physicians/radiologists identified the lesions and assigned each to an exact anatomic location. The image quality, alignment, and confidence in anatomic localization of lesions were scored on a scale of 1-3 for PET/CT and PET/MR imaging. Quantitative analysis was performed by comparing the standardized uptake values. Intraclass correlation coefficients and the Wilcoxon signed-rank test were used to assess intra- and interobserver agreement in image quality, alignment, and confidence in lesion localization for the 2 modalities. RESULTS: Two hundred twenty-seven tracer-avid lesions were identified in 50 patients. Of these, 225 were correctly identified on PET/CT and 227 on PET/MR imaging by all 3 observers. The confidence in anatomic localization improved by 5.1% when using PET/MR imaging, compared with PET/CT. The mean percentage interobserver agreement was 96% for PET/CT and 99% for PET/MR imaging, and intraobserver agreement in lesion localization across the 2 modalities was 93%. There was 10% (5/50 patients) improvement in local staging with PET/MR imaging, compared with PET/CT. CONCLUSION: In this first study, we show the effectiveness of whole-body PET/MR imaging in oncology. There is no statistically significant difference between PET/MR imaging and PET/CT in respect of confidence and degree of inter- and intraobserver agreement in anatomic lesion localization. The PET data on both modalities were similar; however, the observed superior soft-tissue resolution of MR imaging in head and neck, pelvis, and colorectal cancers and of CT in lung and mediastinal nodal disease points to future tailored use in these locations.

Painful knee prosthesis: can we help with bone SPECT/CT?

OBJECTIVES: The aim of the study was to evaluate the value of single-photon emission computerized tomography/computed tomography (SPECT/CT) in the clinical assessment of painful knee prostheses. MATERIALS AND METHODS: Between 2009 and 2011 we identified 105 patients who had undergone Tc-hydroxydiphosphonate SPECT/CT for painful knee prosthesis. Complete follow-up data were available for 69 patients (50 women and 19 men; mean age, 71 years) with painful knee prostheses (59 total, nine unicompartmental, one patellofemoral) and clinical suspicion of infection or loosening. The imaging test report in conjunction with the clinical data from the patient's notes was used to gauge how useful the test had been in terms of patient management. RESULTS: SPECT/CT confirmed the suspected clinical diagnosis of loosening in nine patients (13%) and of infection in two (2.9%) and identified other causes in 43 patients (62.3%). In 85.5% of patients, SPECT/CT was clinically useful (both positive and negative results), whereas in 14.5% it had no clinical impact on patient management. Revision surgery was performed in 24/69 (34.8%) patients and confirmed the SPECT/CT diagnosis in 21 patients (seven loosening, one infection, two subchondral fractures, two postoperative inflammation and nine patellofemoral osteoarthritis). CONCLUSION: SPECT/CT is a useful tool for the evaluation of painful knee prosthesis in 85.5% of cases and helps in confirming mechanical loosening and in excluding other causes such as infection and patellofemoral osteoarthritis.

A novel videography method for generating crack-extension resistance curves in small bone samples.

Assessment of bone quality is an emerging solution for quantifying the effects of bone pathology or treatment. Perhaps one of the most important parameters characterising bone quality is the toughness behaviour of bone. Particularly, fracture toughness, is becoming a popular means for evaluating bone quality. The method is moving from a single value approach that models bone as a linear-elastic material (using the stress intensity factor, K) towards full crack extension resistance curves (R-curves) using a non-linear model (the strain energy release rate in J-R curves). However, for explanted human bone or small animal bones, there are difficulties in measuring crack-extension resistance curves due to size constraints at the millimetre and sub-millimetre scale. This research proposes a novel "whitening front tracking" method that uses videography to generate full fracture resistance curves in small bone samples where crack propagation cannot typically be observed. Here we present this method on sharp edge notched samples (<1 mm×1 mm×Length) prepared from four human femora tested in three-point bending. Each sample was loaded in a mechanical tester with the crack propagation recorded using videography and analysed using an algorithm to track the whitening (damage) zone. Using the "whitening front tracking" method, full R-curves and J-R curves could be generated for these samples. The curves for this antiplane longitudinal orientation were similar to those found in the literature, being between the published longitudinal and transverse orientations. The proposed technique shows the ability to generate full "crack" extension resistance curves by tracking the whitening front propagation to overcome the small size limitations and the single value approach.

Texture-based quantification of lumbar intervertebral disc degeneration from conventional T2-weighted MRI.

BACKGROUND: Disc degeneration quantification is important for monitoring the effects of new therapeutic methods, such as cell and growth factor therapy. Magnetic resonance (MR) image texture reflects biochemical and structural tissue properties and has been used for differentiating between normal and pathological status in a variety of medical applications. PURPOSE: To investigate the suitability of textural descriptors for the quantification of intervertebral disc degeneration using conventional T2-weighted magnetic resonance images of the lumbar spine. MATERIAL AND METHODS: A 3 Tesla scanner was used, and conventional T2- weighted MR images were obtained, and a total of 255 lumbar discs were analyzed. An atlas-based method was used for segmenting the disc regions from the images. A set of first and second order statistics describing texture of each region were calculated. The validity and reliability of these descriptors for disc degeneration severity quantification was tested through their correlation with patient age and qualitative clinical grading of degeneration severity. Texture quantification results were compared to a widely accepted method for disc degeneration quantification based on the measurement of disc's mean signal intensity. RESULTS: Out of the set of texture descriptors tested, two descriptors quantifying image intensity inhomogeneity, i.e. the grey level standard deviation and co-occurrence derived sum of squares displayed the strongest association to patient age and clinical grading of disc degeneration severity (P<0.001). This is attributed to these inhomogeneity descriptors' capability to capture the progressive loss of nucleus-annulus distinction in the degenerative progress. Statistical analysis indicates that these descriptors can effectively separate between early stages of degeneration. Quantitative measurements are highly repeatable (intraclass correlation >0.98). CONCLUSION: Inhomogeneity descriptors could be a valuable tool for tracking the evolution of disc degeneration and monitoring the response to treatment in a simple, precise and repeatable manner.