A Short Dynamic Scan Method of Measuring Bone Metabolic Flux Using [18F]NaF PET.

[18F]NaF PET measurements of bone metabolic flux (Ki) are conventionally obtained with 60-min dynamic scans analysed using the Hawkins model. However, long scan times make this method expensive and uncomfortable for subjects. Therefore, we evaluated and compared measurements of Ki with shorter scan times analysed with fixed values of the Hawkins model rate constants. The scans were acquired in a trial in 30 postmenopausal women, half treated with teriparatide (TPT) and half untreated. Sixty-minute PET-CT scans of both hips were acquired at baseline and week 12 after injection with 180 MBq [18F]NaF. Scans were analysed using the Hawkins model by fitting bone time-activity curves at seven volumes of interest (VOIs) with a semi-population arterial input function. The model was re-run with fixed rate-constants for dynamic scan times from 0-12 min increasing in 4-min steps up to 0-60 min. Using the Hawkins model with fixed rate-constants, Ki measurements with statistical power equivalent or superior to conventionally analysed 60-min dynamic scans were obtained with scan times as short as 12 min.

Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option. PATIENTS AND METHODS: In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life. RESULTS: Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity. CONCLUSION: Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.

Artificial intelligence in medical imaging: A radiomic guide to precision phenotyping of cardiovascular disease.

ABSTRACT: Rapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification and the assessment of stable or even unstable patients. To date, cardiovascular imaging has lagged behind other fields, such as oncology, in the clinical translational of artificial intelligence (AI)-based approaches. We hereby review the current status of AI in non-invasive cardiovascular imaging, using cardiac CT as a running example of how novel machine learning (ML)-based radiomic approaches can improve clinical care. The integration of ML, deep learning, and radiomic methods has revealed direct links between tissue imaging phenotyping and tissue biology, with important clinical implications. More specifically, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging and CT, as well as lessons that can be learned from other areas. Finally, we propose a scientific framework in order to ensure the clinical and scientific validity of future studies in this novel, yet highly promising field. Still in its infancy, AI-based cardiovascular imaging has a lot to offer to both the patients and their doctors as it catalyzes the transition towards a more precise phenotyping of cardiovascular disease.

The influence of CT and dual-energy X-ray absorptiometry (DXA) bone density on quantitative [18F] sodium fluoride PET.

BACKGROUND: [18F] sodium fluoride PET/CT provides quantitative measures of bone metabolic activity expressed by the parameters standardised uptake value (SUV) and bone plasma clearance (K i) that correlate with measurements of bone formation rate obtained by bone biopsy with double tetracycline labelling. Both SUV and K i relate to the tracer uptake in each millilitre of tissue. In general, the bone region of interest (ROI) includes both mineralised bone {generally with a high concentration of [18F]NaF} and bone marrow (with a much lower concentration), suggesting that correcting SUV and K i for volumetric bone mineral density (vBMD) and measuring them with respect to the tracer uptake in each gram of bone mineral might improve the correlation with the findings of bone biopsy. As a first test of this hypothesis, we looked for positive correlations between SUV and K i values with CT and DXA bone mineral density (BMD) parameters measured in the same ROI. METHODS: A retrospective reanalysis was performed of 63 lumbar spine [18F]NaF PET/CT scans acquired in four earlier studies. The quantitative PET parameters SUV and K i were measured in L1-L4 and Hounsfield units (HU) measured on the CT scans in the same ROI. Spine BMD data was also obtained from DXA scans in the form of areal BMD and used to derive the bone mineral apparent density (BMAD, an estimate of vBMD). Scatter plots were drawn of SUV and K i against HU, BMAD and areal BMD and the Spearman rank correlation coefficients derived for each plot. RESULTS: All correlations were positive and statistically significant. Correlations were highest for HU (SUV: RS =0.513, P<0.0001; K i: RS =0.429, P=0.0005) and lowest for areal BMD (SUV: RS =0.353, P=0.005; K i: RS =0.274, P=0.03). CONCLUSIONS: The results demonstrate significant positive correlations between SUV and K i and vBMD measurements in the form of HU from CT or BMAD and areal BMD from DXA. These findings justify further exploration of the relationship between SUV and K i [18F]NaF PET/CT measurements and CT or DXA measurements of vBMD to examine whether normalization for bone density might improve their correlation with bone metabolic activity as measured by bone biopsy.

Is Response Assessment of Breast Cancer Bone Metastases Better with Measurement of 18F-Fluoride Metabolic Flux Than with Measurement of 18F-Fluoride PET/CT SUV?

Our purpose was to establish whether noninvasive measurement of changes in 18F-fluoride metabolic flux to bone mineral (Ki) by PET/CT can provide incremental value in response assessment of bone metastases in breast cancer compared with SUVmax and SUVmeanMethods: Twelve breast cancer patients starting endocrine treatment for de novo or progressive bone metastases were included. Static 18F-fluoride PET/CT scans were acquired 60 min after injection, before and 8 wk after commencing treatment. Venous blood samples were taken at 55 and 85 min after injection to measure plasma 18F-fluoride activity concentrations, and Ki in individual bone metastases was calculated using a previously validated method. Percentage changes in Ki, SUVmax, and SUVmean were calculated from the same index lesions (≤5 lesions) from each patient. Clinical response up to 24 wk, assessed in consensus by 2 experienced oncologists masked to PET imaging findings, was used as a reference standard. Results: Of the 4 patients with clinically progressive disease (PD), mean Ki significantly increased (>25%) in all, SUVmax in 3, and SUVmean in 2. Of the 8 non-PD patients, Ki decreased or remained stable in 7, SUVmax in 5, and SUVmean in 6. A significant mean percentage increase from baseline for Ki, compared with SUVmax and SUVmean, occurred in the 4 patients with PD (89.7% vs. 41.8% and 43.5%, respectively; P < 0.001). Conclusion: After 8 wk of endocrine treatment for bone-predominant metastatic breast cancer, Ki more reliably differentiated PD from non-PD than did SUVmax and SUVmean, probably because measurement of SUV underestimates fluoride clearance by not considering changes in input function.

Radiomics in esophageal and gastric cancer.

Esophageal, esophago-gastric, and gastric cancers are major causes of cancer morbidity and cancer death. For patients with potentially resectable disease, multi-modality treatment is recommended as it provides the best chance of survival. However, quality of life may be adversely affected by therapy, and with a wide variation in outcome despite multi-modality therapy, there is a clear need to improve patient stratification. Radiomic approaches provide an opportunity to improve tumor phenotyping. In this review we assess the evidence to date and discuss how these approaches could improve outcome in esophageal, esophago-gastric, and gastric cancer.

Does Measurement of First-Order and Heterogeneity Parameters Improve Response Assessment of Bone Metastases in Breast Cancer Compared to SUVmax in [18F]fluoride and [18F]FDG PET?

PURPOSE: To establish whether first-order statistical features from [18F]fluoride and 2-deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) demonstrate incremental value in skeletal metastasis response assessment compared with maximum standardised uptake value (SUVmax). PROCEDURES: Sixteen patients starting endocrine treatment for de novo or progressive breast cancer bone metastases were prospectively recruited to undergo [18F]fluoride and [18F]FDG PET/CT scans before and 8 weeks after treatment. Percentage changes in SUV parameters, metabolic tumour volume (MTV), total lesion metabolism (TLM), standard deviation (SD), entropy, uniformity and absolute changes in kurtosis and skewness, from the same ≤ 5 index lesions, were measured. Clinical response to 24 weeks, assessed by two experienced oncologists blinded to PET/CT imaging findings, was used as a reference standard and associations were made between parameters and progression free and overall survival. RESULTS: [18F]fluoride PET/CT: In four patients (20 lesions) with progressive disease (PD), TLM and kurtosis predicted PD better than SUVmax on a patient basis (4, 4 and 3 out of 4, respectively) and TLM, entropy, uniformity and skewness on a lesion basis (18, 16, 16, 18 and 15 out of 20, respectively). Kurtosis was independently associated with PFS (p = 0.033) and OS (p = 0.008) on Kaplan-Meier analysis. [18F]FDG PET: No parameter provided incremental value over SUVmax in predicting PD or non-PD. TLM was significantly associated with OS (p = 0.041) and skewness with PFS (p = 0.005). Interlesional heterogeneity of response was seen in 11/16 and 8/16 patients on [18F]fluoride and [18F]FDG PET/CT, respectively. CONCLUSION: With [18F]fluoride PET/CT, some first-order features, including those that take into account lesion volume but also some heterogeneity parameters, provide incremental value over SUVmax in predicting clinical response and survival in breast cancer patients with bone metastases treated with endocrine therapy. With [18F]FDG PET/CT, no first-order parameters were more accurate than SUVmax although TLM and skewness were associated with OS and PFS, respectively. Intra-patient heterogeneity of response occurs commonly between metastases with both tracers and most parameters.

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([18F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [18F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [18F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [18F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

Challenges and Promises of PET Radiomics.

PURPOSE: Radiomics describes the extraction of multiple, otherwise invisible, features from medical images that, with bioinformatic approaches, can be used to provide additional information that can predict underlying tumor biology and behavior. METHODS AND MATERIALS: Radiomic signatures can be used alone or with other patient-specific data to improve tumor phenotyping, treatment response prediction, and prognosis, noninvasively. The data describing 18F-fluorodeoxyglucose positron emission tomography radiomics, often using texture or heterogeneity parameters, are increasing rapidly. RESULTS: In relation to radiation therapy practice, early data have reported the use of radiomic approaches to better define tumor volumes and predict radiation toxicity and treatment response. CONCLUSIONS: Although at an early stage of development, with many technical challenges remaining and a need for standardization, promise nevertheless exists that PET radiomics will contribute to personalized medicine, especially with the availability of increased computing power and the development of machine-learning approaches for imaging.

Primary Rectal Cancer: Repeatability of Global and Local-Regional MR Imaging Texture Features.

Purpose To assess the day-to-day repeatability of global and local-regional magnetic resonance (MR) imaging texture features derived from primary rectal cancer. Materials and Methods After ethical approval and patient informed consent were obtained, two pretreatment T2-weighted axial MR imaging studies performed prospectively with the same imaging unit on 2 consecutive days in 14 patients with rectal cancer (11 men [mean age, 61.7 years], three women [mean age, 70.0 years]) were analyzed to extract (a) global first-order statistical histogram and model-based fractal features reflecting the whole-tumor voxel intensity histogram distribution and repeating patterns, respectively, without spatial information and (b) local-regional second-order and high-order statistical texture features reflecting the intensity and spatial interrelationships between adjacent in-plane or multiplanar voxels or regions, respectively. Repeatability was assessed for 46 texture features, and mean difference, 95% limits of agreement, within-subject coefficient of variation (wCV), and repeatability coefficient (r) were recorded. Results Repeatability was better for global parameters than for most local-regional parameters. In particular, histogram mean, median, and entropy, fractal dimension mean and standard deviation, and second-order entropy, homogeneity, difference entropy, and inverse difference moment demonstrated good repeatability, with narrow limits of agreement and wCVs of 10% or lower. Repeatability was poorest for the following high-order gray-level run-length (GLRL) gray-level zone size matrix (GLZSM) and neighborhood gray-tone difference matrix (NGTDM) parameters: GLRL intensity variability, GLZSM short-zone emphasis, GLZSM intensity nonuniformity, GLZSM intensity variability, GLZSM size zone variability, and NGTDM complexity, demonstrating wider agreement limits and wCVs of 50% or greater. Conclusion MR imaging repeatability is better for global texture parameters than for local-regional texture parameters, indicating that global texture parameters should be sufficiently robust for clinical practice. Online supplemental material is available for this article.

The effect of post-injection 18F-FDG PET scanning time on texture analysis of peripheral nerve sheath tumours in neurofibromatosis-1.

BACKGROUND: Texture features are being increasingly evaluated in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) as adjunctive imaging biomarkers in a number of different cancers. Whilst studies have reported repeatability between scans, there have been no studies that have specifically investigated the effect that the time of acquisition post-injection of 18F-FDG has on texture features. The aim of this study was to investigate if texture features change between scans performed at different time points post-injection. RESULTS: Fifty-four patients (30 male, 24 female, mean age 35.1 years) with neurofibromatosis-1 and suspected malignant transformation of a neurofibroma underwent 18F-FDG PET/computed tomography (CT) scans at 101.5 ± 15.0 and 251.7 ± 18.4 min post-injection of 350 MBq 18F-FDG to a standard clinical protocol. Following tumour segmentation on both early and late scans, first- (n = 37), second- (n = 25) and high-order (n = 31) statistical features, as well as fractal texture features (n = 6), were calculated and a comparison was made between the early and late scans for each feature. Of the 54 tumours, 30 were benign and 24 malignant on histological analysis or on clinical follow-up for at least 5 years. Overall, 25/37 first-order, 9/25 second-order, 13/31 high-order and 3/6 fractal features changed significantly (p < 0.05) between early and late scans. The corresponding proportions for the 30 benign tumours alone were 22/37, 7/25, 8/31 and 2/6 and for the 24 malignant tumours, 11/37, 6/25, 8/31 and 0/6, respectively. CONCLUSIONS: Several texture features change with time post-injection of 18F-FDG. Thus, when comparing texture features in intra- and inter-patient studies, it is essential that scans are obtained at a consistent time post-injection of 18F-FDG.

Magnetic Resonance Imaging (MRI) of Intratumoral Voxel Heterogeneity as a Potential Response Biomarker: Assessment in a HER2+ Esophageal Adenocarcinoma Xenograft Following Trastuzumab and/or Cisplatin Therapy.

We evaluated magnetic resonance imaging (MRI) voxel heterogeneity following trastuzumab and/or cisplatin in a HER2+ esophageal xenograft (OE19) as a potential response biomarker. OE19 xenografts treated with saline (controls), monotherapy, or combined cisplatin and trastuzumab underwent 9.4-T MRI. Tumor MRI parametric maps of T1 relaxation time (pre/post contrast), T2 relaxation time, T2* relaxation rate (R2*), and apparent diffusion coefficient obtained before (TIME0), after 24hours (TIME1), and after 2weeks of treatment (TIME2) were analyzed. Voxel histogram and fractal parameters (from the whole tumor, rim and center, and as a ratio of rim-to-center) were derived. Tumors were stained for immunohistochemical markers of hypoxia (CA-IX), angiogenesis (CD34), and proliferation (Ki-67). Combination therapy reduced xenograft growth rate (relative change, ∆ +0.58±0.43 versus controls, ∆ +4.1±1.0; P=0.008). More spatially homogeneous voxel distribution between the rim to center was noted after treatment for combination therapy versus controls, respectively, for contrast-enhanced T1 relaxation time (90th percentile: ratio 1.00 versus 0.88, P=0.009), T2 relaxation time (mean: 1.00 versus 0.92, P=0.006; median: 0.98 versus 0.91, P=0.006; 75th percentile: 1.02 versus 0.94, P=0.007), and R2* (10th percentile: 0.99 versus 1.26, P=0.003). We found that combination and trastuzumab monotherapy reduced MRI spatial heterogeneity and growth rate compared to the control or cisplatin groups, the former providing adjunctive tumor response information.

Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

Imaging Tumor Response and Tumoral Heterogeneity in Non-Small Cell Lung Cancer Treated With Antiangiogenic Therapy: Comparison of the Prognostic Ability of RECIST 1.1, an Alternate Method (Crabb), and Image Heterogeneity Analysis.

PURPOSE: We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab. MATERIALS AND METHODS: Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression. RESULTS: Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors. CONCLUSIONS: The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.

Imaging body composition in cancer patients: visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome.

UNLABELLED: In recent years, there has been increasing interest in the influence of body composition on oncological patient outcomes. Visceral obesity, sarcopenia and sarcopenic obesity have been identified as adverse factors in cancer patients. Imaging quantification of body composition such as lean muscle mass and fat distribution is a potentially valuable tool. This review describes the following imaging techniques that may be used to assess body composition: dual-energy X-ray absorptiometry (DXA), computed tomography (CT) and magnetic resonance imaging (MRI). CT and MRI are acquired as part of oncological patient care, thus providing an opportunity to integrate body composition assessment into the standard clinical pathway and allowing supportive care to be commenced as appropriate to improve outcome. MAIN MESSAGES: • Sarcopenia, sarcopenic obesity and visceral obesity are adverse prognostic factors in cancer patients. • CT and MRI are the current gold standard in body composition evaluation. • Body composition may affect chemotherapy tolerance and toxicities.

The precision of textural analysis in (18)F-FDG-PET scans of oesophageal cancer.

OBJECTIVES: Measuring tumour heterogeneity by textural analysis in (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) provides predictive and prognostic information but technical aspects of image processing can influence parameter measurements. We therefore tested effects of image smoothing, segmentation and quantisation on the precision of heterogeneity measurements. METHODS: Sixty-four (18)F-FDG PET/CT images of oesophageal cancer were processed using different Gaussian smoothing levels (2.0, 2.5, 3.0, 3.5, 4.0 mm), maximum standardised uptake value (SUVmax) segmentation thresholds (45%, 50%, 55%, 60%) and quantisation (8, 16, 32, 64, 128 bin widths). Heterogeneity parameters included grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRL), neighbourhood grey-tone difference matrix (NGTDM), grey-level size zone matrix (GLSZM) and fractal analysis methods. The concordance correlation coefficient (CCC) for the three processing variables was calculated for each heterogeneity parameter. RESULTS: Most parameters showed poor agreement between different bin widths (CCC median 0.08, range 0.004-0.99). Segmentation and smoothing showed smaller effects on precision (segmentation: CCC median 0.82, range 0.33-0.97; smoothing: CCC median 0.99, range 0.58-0.99). CONCLUSIONS: Smoothing and segmentation have only a small effect on the precision of heterogeneity measurements in (18)F-FDG PET data. However, quantisation often has larger effects, highlighting a need for further evaluation and standardisation of parameters for multicentre studies. KEY POINTS: • Heterogeneity measurement precision in (18) F-FDG PET is influenced by image processing methods. • Quantisation shows large effects on precision of heterogeneity parameters in (18) F-FDG PET/CT. • Smoothing and segmentation show comparatively smaller effects on precision of heterogeneity parameters.

Correction of the slope-intercept method for the measurement of glomerular filtration rate.

OBJECTIVE: Glomerular filtration rate (GFR) is frequently assessed using the slope-intercept method by fitting a single exponential to plasma samples obtained 2-5 h after injection. The body surface area (BSA)-corrected one-pool clearance (CO,BSA) overestimates true GFR (CT,BSA) because it fails to sample the full plasma curve, and values of CT,BSA are usually estimated from CO,BSA using the Brøchner-Mortensen (BM) equation. An improved equation, CT,BSA=CO,BSA/(1+fBSA×CO,BSA), with fBSA a fixed constant, was proposed by Fleming, but subsequently Jødal and Brøchner-Mortensen (JBM) reported that fBSA varies with BSA. We report data for a large group of individuals who underwent GFR investigations with sampling of the full plasma curve. The aims were to validate the JBM equation with independent data and assess whether replacing the BM equation with a BSA-dependent correction based on Fleming's equation can increase the accuracy of the slope-intercept method. METHODS: Plasma data were analysed for 142 children and adults aged 0.6-56 years who underwent technetium-99m-diethylenetriaminepentaacetic acid GFR investigations with blood samples taken between 5 min and 8 h after injection. Values of CO,BSA were calculated using the 2, 3 and 4 h data. Values of CT,BSA were calculated by integrating the plasma curve between 5 min and 4 h and extrapolating the terminal exponential. Individual values of fBSA were calculated using the relationship fBSA=1/CT,BSA-1/CO,BSA. Nonlinear regression was used to fit the function fBSA=f1×BSA and find the best-fit values for f1 and n. Scatter and Bland-Altman plots were drawn comparing the various formulae for correcting slope-intercept GFR. RESULTS: The trend for fBSA to decrease with increasing BSA was highly significant (Spearman's test: RS=-0.31; P=0.0002). When the data were fitted by nonlinear regression, the best-fit values (95% confidence interval) of the model parameters were n=-0.13 (from -0.21 to -0.04) and f1=0.00191 (from 0.00183 to 0.00200). CONCLUSION: The results confirm that fBSA varies with BSA and provide independent values of the parameters f1 and n. Differences from GFRs calculated using the original JBM equation were small and not clinically significant. The BM equation also performed well for CT,BSA less than 125 ml/min/1.73 m. However, there was a small number of children with CT,BSA greater than 150 ml/min/1.73 m for whom the JBM formula provided more accurate estimates of true GFR than did the BM equation.

Imaging of site specific bone turnover in osteoporosis using positron emission tomography.

The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission tomography ((18)F-NaF PET) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. (18)F-NaF PET provides a novel and noninvasive method of studying site-specific bone formation at the hip and spine, as well as areas of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers and bone biopsy as a tool to investigate new treatments for osteoporosis, and holds promise of a future role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing (18)F-NaF PET scan data, and outlines a simplified approach that uses 5-minute static PET scan images combined with venous blood samples to estimate (18)F-NaF plasma clearance at multiple sites in the skeleton with a single injection of tracer.

Correcting (18)F-fluoride PET static scan measurements of skeletal plasma clearance for tracer efflux from bone.

OBJECTIVE: The aim of the study was to examine whether (18)F-fluoride PET ((18)F-PET) static scan measurements of bone plasma clearance (Ki) can be corrected for tracer efflux from bone from the time of injection. MATERIALS AND METHODS: The efflux of tracer from bone mineral to plasma was described by a first-order rate constant kloss. A modified Patlak analysis was applied to 60-min dynamic (18)F-PET scans of the spine and hip acquired during trials on the bone anabolic agent teriparatide to find the best-fit values of kloss at the lumbar spine, total hip and femoral shaft. The resulting values of kloss were used to extrapolate the modified Patlak plots to 120 min after injection and derive a sequence of static scan estimates of Ki at 4-min intervals that were compared with the Patlak Ki values from the 60-min dynamic scans. A comparison was made with the results of the standard static scan analysis, which assumes kloss=0. RESULTS: The best-fit values of kloss for the spine and hip regions of interest averaged 0.006/min and did not change when patients were treated with teriparatide. Static scan values of Ki calculated using the modified analysis with kloss=0.006/min were independent of time between 10 and 120 min after injection and were in close agreement with findings from the dynamic scans. In contrast, by 2 h after injection the static scan Ki values calculated using the standard analysis underestimated the dynamic scan results by 20%. CONCLUSION: Using a modified analysis that corrects for F efflux from bone, estimates of Ki from static PET scans can be corrected for time up to 2 h after injection. This simplified approach may obviate the need to perform dynamic scans and hence shorten the scanning procedure for the patient and reduce the cost of studies. It also enables reliable estimates of Ki to be obtained from multiple skeletal sites with a single injection of tracer.

(18)F-fluoride positron emission tomography measurements of regional bone formation in hemodialysis patients with suspected adynamic bone disease.

(18)F-fluoride positron emission tomography ((18)F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an (18)F-PET scan, and bone plasma clearance, K i, was measured at ten skeletal regions of interest (ROI). Fifteen subjects had a transiliac bone biopsy following double tetracycline labeling. Two CKD5D patients had ABD confirmed by biopsy. There was significant heterogeneity in K i between skeletal sites, ranging from 0.008 at the forearm to 0.028 mL/min/mL at the spine in the CKD5D group. There were no significant differences in K i between the two study groups or between the two subjects with ABD and the other CKD5D subjects at any skeletal ROI. Five biopsies from the CKD5D patients had single tetracycline labels only, including the two with ABD. Using an imputed value of 0.3 µm/day for mineral apposition rate (MAR) for biopsies with single labels, no significant correlations were observed between lumbar spine K i corrected for BMAD (K i/BMAD) and bone formation rate (BFR/BS), or MAR. When biopsies with single labels were excluded, a significant correlation was observed between K i/BMAD and MAR (r = 0.81, p = 0.008) but not BFR/BS. Further studies are required to establish the sensitivity of (18)F-PET as a diagnostic tool for identifying CKD patients with ABD.