Evaluation of dental maturity in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis.

OBJECTIVES: To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis, compared with a Dutch control group without syndromes. MATERIALS AND METHODS: This study included 60 patients (38 patients with Muenke syndrome, 17 patients with Saethre-Chotzen syndrome, and 5 with TCF12-related craniosynostosis), aged 5.8-16.8 years that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care, and Orthodontics, in Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands. Dental age was calculated according to Demirjian's index of dental maturity. The control group included 451 children without a syndrome. RESULTS: Compared with the control group, dental development was delayed by an average of one year in 5- to 8-year-old patients with Muenke syndrome (P = 0.007) and in 8- to 10-year-old patients with Saethre-Chotzen syndrome (P = 0.044), but not in patients with TCF12-related craniosynostosis. CONCLUSIONS: Our results indicated that dental development was delayed by one year, on average, in patients with Muenke syndrome and Saethre-Chotzen syndrome, compared with a Dutch control group without syndromes. IMPLICATIONS: Our findings have improved the understanding of dental development in patients with Muenke and Saethre-Chotzen syndrome. These results can provide guidance on whether the orthodontist needs to consider growth disturbances related to dental development.

The effect of using a mobile application ("WhiteTeeth") on improving oral hygiene: A randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of the WhiteTeeth mobile app, a theory-based mobile health (mHealth) program for promoting oral hygiene in adolescent orthodontic patients. METHODS: In this parallel randomized controlled trial, the data of 132 adolescents were collected during three orthodontic check-ups: at baseline (T0), at 6-week follow-up (T1) and at 12-week follow-up (T2). The intervention group was given access to the WhiteTeeth app in addition to usual care (n = 67). The control group received usual care only (n = 65). The oral hygiene outcomes were the presence and the amount of dental plaque (Al-Anezi and Harradine plaque index), and the total number of sites with gingival bleeding (Bleeding on Marginal Probing Index). Oral health behaviour and its psychosocial factors were measured through a digital questionnaire. We performed linear mixed-model analyses to determine the intervention effects. RESULTS: At 6-week follow-up, the intervention led to a significant decrease in gingival bleeding (B = -3.74; 95% CI -6.84 to -0.65) and an increase in the use of fluoride mouth rinse (B = 1.93; 95% CI 0.36 to 3.50). At 12-week follow-up, dental plaque accumulation (B = -11.32; 95% CI -20.57 to -2.07) and the number of sites covered with plaque (B = -6.77; 95% CI -11.67 to -1.87) had been reduced significantly more in the intervention group than in the control group. CONCLUSIONS: The results show that adolescents with fixed orthodontic appliances can be helped to improve their oral hygiene when usual care is combined with a mobile app that provides oral health education and automatic coaching. Netherlands Trial Registry Identifier: NTR6206: 20 February 2017.

Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC Imaging Group.

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further metastatic progression, thus increasing overall survival. Metastasis-directed therapies require imaging methods that definitively recognise oligometastatic disease to validate their efficacy and reliably monitor response, particularly so that morbidity associated with inappropriately treating disease subsequently recognised as polymetastatic can be avoided. In this Review, we assess imaging methods used to identify metastatic prostate cancer at first diagnosis, at biochemical recurrence, or at the castration-resistant stage. Standard imaging methods recommended by guidelines have insufficient diagnostic accuracy for reliably diagnosing oligometastatic disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers (choline or prostate-specific membrane antigen ligand), and increasingly whole-body MRI with diffusion-weighted imaging, allow earlier and more precise identification of metastases. The European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to integrate modern imaging methods into the care pathway at the various stages of prostate cancer to identify oligometastatic disease. The EORTC proposes clinical trials that use modern imaging methods to evaluate the benefits of metastasis-directed therapies.

Estimating the arterial input function from dynamic contrast-enhanced MRI data with compensation for flow enhancement (II): Applications in spine diagnostics and assessment of crohn's disease.

BACKGROUND: Pharmacokinetic (PK) models can describe microvascular density and integrity. An essential component of PK models is the arterial input function (AIF) representing the time-dependent concentration of contrast agent (CA) in the blood plasma supplied to a tissue. PURPOSE/HYPOTHESIS: To evaluate a novel method for subject-specific AIF estimation that takes inflow effects into account. STUDY TYPE: Retrospective study. SUBJECTS: Thirteen clinical patients referred for spine-related complaints; 21 patients from a study into luminal Crohn's disease with known Crohn's Disease Endoscopic Index of Severity (CDEIS). FIELD STRENGTH/SEQUENCE: Dynamic fast spoiled gradient echo (FSPGR) at 3T. ASSESSMENT: A population-averaged AIF, AIFs derived from distally placed regions of interest (ROIs), and the new AIF method were applied. Tofts' PK model parameters (including vp and Ktrans ) obtained with the three AIFs were compared. In the Crohn's patients Ktrans was correlated to CDEIS. STATISTICAL TESTS: The median values of the PK model parameters from the three methods were compared using a Mann-Whitney U-test. The associated variances were statistically assessed by the Brown-Forsythe test. Spearman's rank correlation coefficient was computed to test the correlation of Ktrans to CDEIS. RESULTS: The median vp was significantly larger when using the distal ROI approach, compared to the two other methods (P < 0.05 for both comparisons, in both applications). Also, the variances in vp were significantly larger with the ROI approach (P < 0.05 for all comparisons). In the Crohn's disease study, the estimated Ktrans parameter correlated better with the CDEIS (r = 0.733, P < 0.001) when the proposed AIF was used, compared to AIFs from the distal ROI method (r = 0.429, P = 0.067) or the population-averaged AIF (r = 0.567, P = 0.011). DATA CONCLUSION: The proposed method yielded realistic PK model parameters and improved the correlation of the Ktrans parameter with CDEIS, compared to existing approaches. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2018;47:1197-1204.

Study protocol of a randomized controlled trial to test the effect of a smartphone application on oral-health behavior and oral hygiene in adolescents with fixed orthodontic appliances.

BACKGROUND: Adolescents with fixed orthodontic appliances are at high risk of developing dental caries. To date, new smartphone technologies have seldom been used to support them in the preventive behavior that can help prevent dental caries. After an intervention-mapping process, we developed a smartphone application (the WhiteTeeth app) for preventing dental caries through improved oral-health behavior and oral hygiene. The app, which is intended to be used at home, will help adolescents with fixed orthodontic appliances perform their oral self-care behavior. The app is based on the Health Action Process Approach (HAPA) theory, and incorporates several behavior-change techniques that target the psychosocial factors of oral-health behavior. This article describes the protocol of a randomized controlled trial (RCT) to evaluate the effects of the WhiteTeeth app on oral-health behavior and oral-hygiene outcomes (presence of dental plaque and gingival bleeding) compared with those of care as usual, in patients aged 12-16 with fixed orthodontic appliances. METHODS/DESIGN: The RCT has two conditions: an experimental group that will receive the WhiteTeeth app in addition to care as usual, and a control group that will only receive care as usual. Care as usual will include routine oral-health education and instruction at orthodontic check-ups. In the western part of the Netherlands 146 participants will be recruited from four orthodontic clinics. Data will be collected during three orthodontic check-ups: baseline (T0), 6 weeks of follow-up (T1) and 12 weeks of follow-up (T2). The primary study outcomes are the presence of dental plaque (measured with a modified Silness and Loë Plaque Index); and gingival bleeding (measured with the Bleeding on Marginal Probing Index). Secondary outcomes include changes in self-reported oral-health behaviors and its psychosocial factors identified by the HAPA theory, such as outcome expectancies, intention, action self-efficacy, coping planning and action control. DISCUSSION: Since the intervention was designed to target psychosocial factors in the motivational and volitional components of the behavior-change process, we hypothesize that the app will cause greater improvements in oral-health behavior and oral hygiene more than traditional oral-health-promotion programs (i.e., care as usual). TRIAL REGISTRATION: The trial has been registered with the Dutch Trial Register ( NTR6206 : 20 February 2017).

Permanent tooth agenesis in non-syndromic Robin sequence and cleft palate: prevalence and patterns.

OBJECTIVES: Partial tooth agenesis is frequently observed in Robin sequence. Tooth anomalies are increasingly considered as an extended phenotype of the cleft palate population. The study objective was to compare the prevalence and patterns of tooth agenesis in a group of patients with non-syndromic Robin sequence (ns-RS) and a group with non-syndromic cleft palate (ns-CP). MATERIALS AND METHODS: The panoramic radiographs of 115 ns-RS and 191 ns-CP patients were assessed for agenesis of the permanent dentition (excluding third molars) and the patterns recorded using the Tooth Agenesis Code. RESULTS: Partial tooth agenesis was observed in 47.8% of ns-RS and 29.8% of ns-CP patients with a greater prevalence in the mandibula than in the maxilla, particularly in ns-RS. The teeth most frequently absent in both groups were the mandibular second premolars and maxillary lateral incisors. Tooth agenesis was bilateral in two-thirds of affected ns-RS patients and one-half of ns-CP patients. In ns-RS, bilateral agenesis of the mandibular second premolars was more frequently observed in female than that in male patients. Completely symmetrical patterns of hypodontia were found in around 45% of ns-RS patients with tooth agenesis compared to 35% in ns-CP. No association was found between the extent of the palatal cleft and the severity of hypodontia. CONCLUSION: Tooth agenesis is more prevalent in ns-RS than that in ns-CP, demonstrates a much greater predilection for the mandible in ns-RS, and bears no relation to the extent of the palatal cleft. CLINICAL RELEVANCE: When compared to ns-CP, additional developmental disturbances are likely involved in the etiology of tooth agenesis in ns-RS. Future research could help identify the underlying genetic traits and aid in classifying patients in those with and without expected tooth agenesis in order to facilitate orthodontic management strategies.

The Development of the Cleft Aesthetic Rating Scale: A New Rating Scale for the Assessment of Nasolabial Appearance in Complete Unilateral Cleft Lip and Palate Patients.

OBJECTIVE: The development of the Cleft Aesthetic Rating Scale, a simple and reliable photographic reference scale for the assessment of nasolabial appearance in complete unilateral cleft lip and palate patients. DESIGN: A blind retrospective analysis of photographs of cleft lip and palate patients was performed with this new rating scale. SETTING: VU Medical Center Amsterdam and the Academic Center for Dentistry of Amsterdam. PATIENTS: Complete unilateral cleft lip and palate patients at the age of 6 years. MAIN OUTCOME MEASURES: Photographs that showed the highest interobserver agreement in earlier assessments were selected for the photographic reference scale. Rules were attached to the rating scale to provide a guideline for the assessment and improve interobserver reliability. Cropped photographs revealing only the nasolabial area were assessed by six observers using this new Cleft Aesthetic Rating Scale in two different sessions. RESULTS: Photographs of 62 children (6 years of age, 44 boys and 18 girls) were assessed. The interobserver reliability for the nose and lip together was 0.62, obtained with the intraclass correlation coefficient. To measure the internal consistency, a Cronbach alpha of .91 was calculated. The estimated reliability for three observers was .84, obtained with the Spearman Brown formula. CONCLUSION: A new, easy to use, and reliable scoring system with a photographic reference scale is presented in this study.

Patterns of tooth agenesis in patients with orofacial clefts.

Orofacial clefts are a common oral disorder associated with tooth agenesis. As information on the simultaneous absence of teeth can be an aid in treatment planning, a large sample of orofacial cleft patients was examined. The sample consisted of 910 patients with cleft lip and palate. Tooth agenesis was assessed on the basis of at least two panoramic radiographs and patient records. Third-molar agenesis was determined in 474 patients. Patterns of tooth agenesis were analysed using Tooth Agenesis Code (TAC) values, according to VAN WIJK & TAN. Per quadrant, at least 90% of patients could be described according to three different patterns. In the maxilla, 85% of patients with tooth agenesis had a TAC-value of 2, 16, or 18 on either the left side, right side or bilaterally. In the mandible, 90% of patients with tooth agenesis had a TAC-value of 16, 1 or 2 on either the left side, right side or bilaterally. In patients with tooth agenesis, patterns were symmetrical in the maxilla in 18.8% and in the mandible in 51%. More extended cleft types were associated with a higher prevalence of tooth agenesis. Third-molar agenesis (prevalence = 22.4%) was significantly related to the prevalence of other absent teeth. These results show which patterns of tooth agenesis can be expected to occur in most orofacial cleft patients.

Repeatability of two semi-automatic artificial intelligence approaches for tumor segmentation in PET.

BACKGROUND: Positron emission tomography (PET) is routinely used for cancer staging and treatment follow-up. Metabolic active tumor volume (MATV) as well as total MATV (TMATV-including primary tumor, lymph nodes and metastasis) and/or total lesion glycolysis derived from PET images have been identified as prognostic factor or for the evaluation of treatment efficacy in cancer patients. To this end, a segmentation approach with high precision and repeatability is important. However, the implementation of a repeatable and accurate segmentation algorithm remains an ongoing challenge. METHODS: In this study, we compare two semi-automatic artificial intelligence (AI)-based segmentation methods with conventional semi-automatic segmentation approaches in terms of repeatability. One segmentation approach is based on a textural feature (TF) segmentation approach designed for accurate and repeatable segmentation of primary tumors and metastasis. Moreover, a convolutional neural network (CNN) is trained. The algorithms are trained, validated and tested using a lung cancer PET dataset. The segmentation accuracy of both segmentation approaches is compared using the Jaccard coefficient (JC). Additionally, the approaches are externally tested on a fully independent test-retest dataset. The repeatability of the methods is compared with those of two majority vote (MV2, MV3) approaches, 41%SUVMAX, and a SUV > 4 segmentation (SUV4). Repeatability is assessed with test-retest coefficients (TRT%) and intraclass correlation coefficient (ICC). An ICC > 0.9 was regarded as representing excellent repeatability. RESULTS: The accuracy of the segmentations with the reference segmentation was good (JC median TF: 0.7, CNN: 0.73). Both segmentation approaches outperformed most other conventional segmentation methods in terms of test-retest coefficient (TRT% mean: TF: 13.0%, CNN: 13.9%, MV2: 14.1%, MV3: 28.1%, 41%SUVMAX: 28.1%, SUV4: 18.1%) and ICC (TF: 0.98, MV2: 0.97, CNN: 0.99, MV3: 0.73, SUV4: 0.81, and 41%SUVMAX: 0.68). CONCLUSION: The semi-automatic AI-based segmentation approaches used in this study provided better repeatability than conventional segmentation approaches. Moreover, both algorithms lead to accurate segmentations for both primary tumors as well as metastasis and are therefore good candidates for PET tumor segmentation.

The effect of lip closure on palatal growth in patients with unilateral clefts.

OBJECTIVES: The objective of this study was to compare maxillary dimensions and growth in newborns with Complete Unilateral Cleft Lip and Palate (UCLP) to healthy newborns before and after cheiloplasty. Additionally, a palatal growth curve is constructed to give more information about the natural growth before surgical intervention. METHODS: Twenty-eight newborns with complete UCLP were enrolled in this study. Multiple plaster-casts of each child during their first year were collected and grouped in before and after cheiloplasty. A previous developed semi-automatic segmentation tool was used to assess the maxillary dimensions and were compared to a healthy control group. Z-scores were calculated to indicate differences between the two populations and if cheiloplasty had influence on maxillary growth. Furthermore, the prediction model created in a previous study was used to indicate differences between predictions and the outcome in UCLP measurements. The analysis was tested for inter- and intra-observer variability. RESULTS: Results show differences in alveolar and palatal shape in UCLP patients in comparison with healthy controls. Prior to cheiloplasty an increased width and alveolar length was observed while the palatal depth was decreased. After cheiloplasty the widths moved towards normal but were still significantly larger. CONCLUSION: Infants with unilateral cleft lip and palate show a wider maxillary arch in comparison with the control population. Initial treatment has most influence on the width of the arch, which decreased towards normal.

PET segmentation of bulky tumors: Strategies and workflows to improve inter-observer variability.

BACKGROUND: PET-based tumor delineation is an error prone and labor intensive part of image analysis. Especially for patients with advanced disease showing bulky tumor FDG load, segmentations are challenging. Reducing the amount of user-interaction in the segmentation might help to facilitate segmentation tasks especially when labeling bulky and complex tumors. Therefore, this study reports on segmentation workflows/strategies that may reduce the inter-observer variability for large tumors with complex shapes with different levels of user-interaction. METHODS: Twenty PET images of bulky tumors were delineated independently by six observers using four strategies: (I) manual, (II) interactive threshold-based, (III) interactive threshold-based segmentation with the additional presentation of the PET-gradient image and (IV) the selection of the most reasonable result out of four established semi-automatic segmentation algorithms (Select-the-best approach). The segmentations were compared using Jaccard coefficients (JC) and percentage volume differences. To obtain a reference standard, a majority vote (MV) segmentation was calculated including all segmentations of experienced observers. Performed and MV segmentations were compared regarding positive predictive value (PPV), sensitivity (SE), and percentage volume differences. RESULTS: The results show that with decreasing user-interaction the inter-observer variability decreases. JC values and percentage volume differences of Select-the-best and a workflow including gradient information were significantly better than the measurements of the other segmentation strategies (p-value<0.01). Interactive threshold-based and manual segmentations also result in significant lower and more variable PPV/SE values when compared with the MV segmentation. CONCLUSIONS: FDG PET segmentations of bulky tumors using strategies with lower user-interaction showed less inter-observer variability. None of the methods led to good results in all cases, but use of either the gradient or the Select-the-best workflow did outperform the other strategies tested and may be a good candidate for fast and reliable labeling of bulky and heterogeneous tumors.

Evaluation of diffusion-weighted MRI and (18F) fluorothymidine-PET biomarkers for early response assessment in patients with operable non-small cell lung cancer treated with neoadjuvant chemotherapy.

OBJECTIVE: To correlate changes in the apparent diffusion coefficient (ADC) from diffusion-weighted (DW)-MRI and standardised uptake value (SUV) from fluorothymidine (18FLT)-PET/CT with histopathological estimates of response in patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy and track longitudinal changes in these biomarkers in a multicentre, multivendor setting. METHODS: 14 patients with operable NSCLC recruited to a prospective, multicentre imaging trial (EORTC-1217) were treated with platinum-based neoadjuvant chemotherapy. 13 patients had DW-MRI and FLT-PET/CT at baseline (10 had both), 12 were re-imaged at Day 14 (eight dual-modality) and nine after completing chemotherapy, immediately before surgery (six dual-modality). Surgical specimens (haematoxylin-eosin and Ki67 stained) estimated the percentage of residual viable tumour/necrosis and proliferation index. RESULTS: Despite the small numbers,significant findings were possible. ADCmedian increased (p < 0.001) and SUVmean decreased (p < 0.001) significantly between baseline and Day 14; changes between Day 14 and surgery were less marked. All responding tumours (>30% reduction in unidimensional measurement pre-surgery), showed an increase at Day 14 in ADC75th centile and reduction in total lesion proliferation (SUVmean x proliferative volume) greater than established measurement variability. Change in imaging biomarkers did not correlate with histological response (residual viable tumour, necrosis). CONCLUSION: Changes in ADC and FLT-SUV following neoadjuvant chemotherapy in NSCLC were measurable by Day 14 and preceded changes in unidimensional size but did not correlate with histopathological response. However, the magnitude of the changes and their utility in predicting (non-) response (tumour size/clinical outcome) remains to be established. ADVANCES IN KNOWLEDGE: During treatment, ADC increase precedes size reductions, but does not reflect histopathological necrosis.

Healthy Tissue Uptake of 68Ga-Prostate-Specific Membrane Antigen, 18F-DCFPyL, 18F-Fluoromethylcholine, and 18F-Dihydrotestosterone.

PET is increasingly used for prostate cancer (PCa) diagnostics. Important PCa radiotracers include 68Ga-prostate-specific membrane antigen HBED-CC (68Ga-PSMA), 18F-DCFPyL, 18F-fluoromethylcholine (18F-FCH), and 18F-dihydrotestosterone (18F-FDHT). Knowledge on the variability of tracer uptake in healthy tissues is important for accurate PET interpretation, because malignancy is suspected only if the uptake of a lesion contrasts with its background. Therefore, the aim of this study was to quantify uptake variability of PCa tracers in healthy tissues and identify stable reference regions for PET interpretation. Methods: A total of 232 PCa PET/CT scans from multiple hospitals was analyzed, including 87 68Ga-PSMA scans, 50 18F-DCFPyL scans, 68 18F-FCH scans, and 27 18F-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow, and muscle using several SUVs (SUVmax, SUVmean, SUVpeak). Variability in uptake between patients was analyzed using the coefficient of variation (COV%). For all tracers, SUV reference ranges (95th percentiles) were calculated, which could be applicable as image-based quality control for future PET acquisitions. Results: For 68Ga-PSMA, the lowest uptake variability was observed in the blood pool (COV, 19.9%), which was significantly more stable than all other tissues (COV, 29.8%-35.2%; P = 0.001-0.024). For 18F-DCFPyL, the lowest variability was observed in the blood pool and liver (COV, 14.4% and 21.7%, respectively; P = 0.001-0.003). The least variable 18F-FCH uptake was observed in the liver, blood pool, and bone marrow (COV, 16.8%-24.2%; P = 0.001-0.012). For 18F-FDHT, low uptake variability was observed in all tissues, except the lung (COV, 14.6%-23.6%; P = 0.001-0.040). The different SUV types had limited effect on variability (COVs within 3 percentage points). Conclusion: In this multicenter analysis, healthy tissues with limited uptake variability were identified, which may serve as reference regions for PCa PET interpretation. These reference regions include the blood pool for 68Ga-PSMA and 18F-DCFPyL and the liver for 18F-FCH and 18F-FDHT. Healthy tissue SUV reference ranges are presented and applicable as image-based quality control.

Reproducibility and Repeatability of Semiquantitative 18F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study.

18F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) 18F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of 18F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 18F-FDHT-avid regions were included. The best repeatability among 18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R2 ≥ 0.92; ICC ≥ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUVpeak) to 24.6% (SUVmax). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated (R2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%-10.8%). Conclusion: Uptake metrics derived from 18F-FDHT PET/CT show high repeatability and interobserver reproducibility.

MRI protocol optimization for quantitative DCE-MRI of the spine.

PURPOSE: In this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM). MATERIALS AND METHODS: In 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2ml/kg body weight) was injected intravenously at a speed of 3ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T1 map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model. RESULTS: Sagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T2* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient-echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5mm and two acquisitions. CONCLUSION: The proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.

Repeatability of Quantitative 18F-Fluoromethylcholine PET/CT Studies in Prostate Cancer.

UNLABELLED: Repeatable quantification is essential when using (18)F-fluoromethylcholine PET/CT to monitor treatment response in prostate cancer. It has been shown that SUV normalized to the area under the blood activity concentration curve (SUVAUC) provides a better correlation with full kinetic analysis than does standard SUV. However, the precision of SUVAUC is not known yet. The purpose of this study was to assess the repeatability of various semiquantitative (18)F-fluoromethylcholine parameters in prostate cancer. METHODS: Twelve patients (mean age ± SD, 64 ± 8 y) with metastasized prostate cancer underwent two sets of (18)F-fluoromethylcholine PET/CT scans, on consecutive days. Each set consisted of a 30-min dynamic PET/CT scan of the chest after intravenous administration of 200 MBq of (18)F-fluoromethylcholine, followed by a whole-body PET/CT scan at 40 min. The dynamic scan was used to derive the area under the blood activity concentration curve. Lesion uptake was derived from the whole-body scan using various types of volumes of interest: maximum, peak, and mean. Each of these parameters was normalized to injected activity per body weight, area under the blood activity concentration curve, and blood concentration itself at 40 min, resulting in several types of SUVs: SUV, SUVAUC, and SUVTBR The test-retest repeatability of these metrics, as well as metabolic tumor volume (MTV) and total uptake of choline in the lesion, were studied. The level of agreement between test-retest data and reliability was assessed using Bland-Altman plots, repeatability coefficients, and intraclass correlation coefficients (ICCs). RESULTS: A total of 67 choline-avid metastases were identified: 44 bone lesions and 23 lymph node lesions. In the case of SUVmax, the repeatability coefficients for SUV, SUVAUC, and SUVTBR were 26% (ICC, 0.95), 31% (ICC, 0.95), and 46% (ICC, 0.89), respectively. Similar values were obtained for SUVpeak and SUVmean The repeatability of SUVAUC was comparable to that of SUVmax, SUVpeak, and SUVmean. Tissue type and tumor localization did not affect repeatability. An MTV of less than 4.2 cm(3) had larger variability than larger volumes (repeatability coefficient, 45% vs. 29%; P = 0.048). The repeatability coefficient did not significantly differ between lesions with SUVpeak above or below the median value of 8.3 (19% vs. 28%; P = 0.264). CONCLUSION: The repeatability of SUVAUC was comparable to that of standard SUV. The repeatability coefficients of various semiquantitative (18)F-fluoromethylcholine parameters (SUV, MTV, and total uptake in the lesion) were approximately 35%. Larger differences are likely to represent treatment effects.

Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with ¹8F-Fluoroazomycin Arabinoside and ¹5O-H2O PET.

UNLABELLED: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) is a PET tracer of tumor hypoxia. However, as hypoxia often is associated with decreased perfusion, the delivery of (18)F-FAZA may be compromised, potentially disturbing the association between tissue hypoxia and (18)F-FAZA uptake. The aim of this study was to gain insight into the relationship between tumor perfusion and (18)F-FAZA uptake. METHODS: Ten patients diagnosed with advanced non-small cell lung cancer underwent subsequent dynamic (15)O-H2O and (18)F-FAZA PET scans with arterial sampling. Parametric images of both (15)O-H2O-derived perfusion (tumor blood flow [TBF]) and volume of distribution (V(T)) of (18)F-FAZA were generated. Next, multiparametric classification was performed using lesional and global thresholds. Voxels were classified as low or high TBF and (18)F-FAZA V(T), respectively. Finally, by combining these initial classifications, voxels were allocated to 4 categories: lowTBF-lowV(T), lowTBF-highV(T), highTBF-lowV(T), and highTBF-highV(T). RESULTS: A total of 13 malignant lesions were identified in the 10 patients. The TBF and (18)F-FAZA V(T) values (average ± SD) across all lesions were 0.45 ± 0.20 mL·cm(-3)·min(-1) and 0.94 ± 0.31 mL·cm(-3), respectively. The averages of all lesional median values for TBF and (18)F-FAZA V(T) were 0.37 ± 0.15 mL·cm(-3)·min(-1) and 0.85 ± 0.18 mL·cm(-3), respectively. Multiparametric analysis showed that classified voxels were clustered rather than randomly distributed. Several intralesion areas were identified where (18)F-FAZA V(T) was inversely related to TBF. On the other hand, there were also distinct areas where TBF as well as (18)F-FAZA V(T) were decreased or increased. CONCLUSION: The present data indicate that spatial variation of (18)F-FAZA uptake is not necessarily inversely related to TBF. This suggests that decreased TBF may result in flow-limited delivery of (18)F-FAZA. Areas with both high (18)F-FAZA uptake and high TBF values suggest that high (18)F-FAZA uptake, possibly suggesting hypoxia, may occur despite high TBF values. In conclusion, multiparametric evaluation of the spatial distributions of both TBF and (18)F-FAZA uptake may be helpful for understanding the (18)F-FAZA signal.