99mTc-hydroxymethylene Diphosphonate Research Articles

DON’T FORGET ABOUT CARDIAC AMYLOIDOSIS: WHEN RED FLAGS MATTER

Abstract Case Report A 78–year–old man came to our attention for worsening dyspnea, asthenia and frequent lipothymic episodes in the last few weeks. Nothing remarkable was reported in anamnesis except for periodic cardiological check–ups ascribed to hypertensive heart disease and moderate aortic stenosis. Other cardiovascular risk factors were obesity, previous smoking habits and dyslipidemia. A recent 24–hours ECG monitoring revealed slow permanent atrial fibrillation (AF) with 3–seconds pauses, frequent premature ventricular complexes (PVCs) and some PVCs couplets. On arrival, NT–proBNP was elevated (2952 pg/mL), while ECG showed AF with a heart rate of 50/m and low voltages in peripheral leads. Transthoracic echocardiogram revealed a biatrial dilatation, a severe left ventricular (LV) concentric hypertrophy with a preserved LV ejection fraction (EF) and a moderate aortic stenosis. In addition, a restrictive LV filling pattern, a decreased longitudinal myocardial contraction and an apical sparing of longitudinal strain were reported. Invasive coronary angiography was performed with evidence of normal coronary arteries. Given the echocardiographic suspicion of amyloidosis, a 99mTc–Hydroxymethylene diphosphonate (HMDP) scintigraphy was performed, showing a moderate cardiac uptake and an attenuated bone uptake (Perugini Score 2). Serum and urine immunofixation resulted negative. Genetic testing did not find any mutations in Transthyretin (TTR) gene. Therefore, the diagnosis of TTR wild–type amyloidosis was made. Before discharge, putting it all together, we opted to implant a leadless pacemaker in order to protect the patient from life–threatening bradyarrhythmias. Discussion Although it is currently considered rare, there is growing evidence that cardiac amyloidosis may be more common than once thought. First of all, it should be investigated in HFpEF–patients (heart failure with preserved EF) with LV hypertrophy. Despite several red flags (low QRS voltages, conduction disorders, elevated NT–proBNP, severe LV hypertrophy and aortic stenosis) and various medical consultations, our patient had to wait 4 years or more to be diagnosed with cardiac amyloidosis. Inevitably, a diagnostic delay means loss of time in treatment initiation. Earlier diagnosis would enable us to improve our patients’ survival and heart failure hospitalization. Awareness alone is not enough, we must be right on target too.

Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study

The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. Pfizer.

Dynamic blood flow imaging with 99mTc-hydroxymethylene diphosphonate as a therapeutic response marker in patients with Raynaud's phenomenon.

We evaluated the predictive value of dynamic blood flow scintigraphy with 99mTc-HDP (hydroxymethylene diphosphonate) for therapeutic response in patients with Raynaud's phenomenon (RP). Eighty patients who underwent dynamic blood flow scintigraphy using the one-hand chilling method were enrolled. We analyzed the quantitative variables as the ratio of chilled fingers to ambient fingers (CAfinger), that of the chilled hand to ambient hand (CAhand), and that of chilled fingers to ambient palm (FPR) (CAFPR) at 15 and 30s after 99mTc-HDP bolus injection. Total cumulative radioactivity counts for 180s were obtained. We evaluated the clinical utility of these quantitative parameters with other clinical variables, including RP severity, therapeutic compliance, types of RP, and scintigraphic interpretation of findings in patients with RP. Fifty-two patients showed poor therapeutic response. There were significant differences between good- and poor-therapeutic responder groups in RP intensity (p = 0.003), CAfinger15s (p = 0.008), CAfinger30s (p = 0.002), CAfinger180s (p = 0.011), CAhand15s (p = 0.008), CAhand30s (p = 0.007), CAhand180s (p = 0.017), CAFPR30s (p = 0.004), and CAFPR180s (p = 0.002). After multivariate logistic regression analysis, only CAfinger30s (p = 0.002) had an independent predictive value of the therapeutic response. 99mTc-HDP dynamic blood flow scintigraphy could be helpful in predicting the therapeutic response in patients with RP.

Cardiac amyloidosis and aortic stenosis: a state-of-the-art review.

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aortic valve replacement. Diagnostic workup for cardiac amyloidosis in patients with aortic stenosis is based on a multi-parametric approach considering clinical assessment, electrocardiogram, haematologic tests, basic and advanced echocardiography, cardiac magnetic resonance, and technetium labelled cardiac scintigraphy like technetium-99 m (99mTc)-pyrophosphate, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, and 99mTc-hydroxymethylene diphosphonate. However, a biopsy is the traditional gold standard for diagnosis. The prognosis of patients with coexisting cardiac amyloidosis and aortic stenosis is still under evaluation. The combination of these two pathologies worsens the prognosis. Regarding treatment, mortality is reduced in patients with cardiac amyloidosis and severe aortic stenosis after undergoing transcatheter aortic valve replacement. Further studies are needed to confirm these findings and to understand whether the diagnosis of cardiac amyloidosis could affect therapeutic strategies. The aim of this review is to critically expose the current state-of-art regarding the association of cardiac amyloidosis with aortic stenosis, from pathophysiology to treatment.

Radiopharmaceutical extravasation in bone scintigraphy: a cross-sectional study.

Tc-99m Hydroxymethylene diphosphonate (HMDP) bone scintigraphy is commonly used to diagnose bone disorders. We aimed to quantify and characterize the occurrence of radiopharmaceutical extravasation in bone scintigraphy, using Tc-99m HMDP, as well as to compare the visual classification of the events with an independent analysis using image processing software. We conducted a cross-sectional study, using data from a total of 400 (9.1%) exams, randomly selected from all the procedures performed in 2018 in the Portuguese Institute of Oncology of Porto, Portugal. Prevalence estimate and the corresponding 95% confidence interval (CI) was computed for the presence of extravasation. Odds ratios and 95% CI were computed to quantify the association between demographic and clinical characteristics, and the occurrence of extravasation. The prevalence of Tc-99m HMDP extravasation was 26.5% (95% CI: 22.4-31.0). Those from an inpatient setting had almost seven-fold higher odds of extravasation than those from an outpatient setting. When the wrist was used for administration, there was three times more odds of extravasation when compared to the use of hand. There were statistically significant differences in the median scores of extravasations severity obtained from image processing software according to the different grades attributed by visual appreciation ( P < 0.001). Tc-99m HMDP extravasation occurred in one out of four patients, being more frequent among those from an inpatient setting and when the wrist was used for administration. Visual appreciation of the extravasation seems to be acceptable to classify its severity.

Negative methylene diphosphonate scintigraphy in biopsy-confirmed hereditary transthyretin Ala117Ser cardiac amyloidosis: a case report

99mTc-pyrophosphate (99mTc-PYP) scintigraphy is highly sensitive and specific for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). Commonly used alternative tracers included 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP). A 61-year-old Chinese man presented with signs indicative of left ventricular hypertrophy. Genetic testing revealed heterozygous transthyretin Ala117Ser mutation. Scintigraphy using 99mTc-methylene diphosphonate failed to show myocardial uptake. Five months later, the patient underwent permanent pacemaker implantation. Tafamidis was used irregularly, and the patient died 2 years later. 99mTc-methylene diphosphonate may not be appropriate for diagnostic use in ATTR-CA patient with transthyretin Ala117Ser mutation.

Alternative Isotope Options for Amyloidosis Imaging: A Technologist’s Perspective

The recent pyrophosphate shortages can limit the availability of 99mTc-pyrophosphate scans for cardiac amyloidosis. However, another radiotracer is available: 99mTc-hydroxymethylene diphosphonate (HMDP). 99mTc-HMDP, widely available in the United States for bone scanning, has effectively been used in Europe to diagnose transthyretin amyloidosis. 99mTc-HMDP and 99mTc-pyrophosphate have comparable blood clearance and sensitivity. The imaging protocols for 99mTc-HMDP and 99mTc-pyrophosphate are similar, except 99mTc-HMDP is imaged 2-3 h after injection and whole-body imaging is optional. The interpretation is also essentially the same; however, caution is needed because of the high soft-tissue uptake with 99mTc-HMDP, which can affect heart-to-contralateral-lung ratios.

A computer program to assess the bone scan index for Tc-99m hydroxymethylene diphosphonate: evaluation of jaw pathologies of patients with bone metastases using SPECT/CT

This study aimed to evaluate the jaw pathologies of patients with bone metastases using a computer program to assess the bone scan index (BSI) for Tc-99m hydroxymethylene diphosphonate (HMDP) with single-photon emission computed tomography/computed tomography (SPECT/CT). Ninety-seven patients with jaw pathologies (24 with bone metastases and 73 without) were evaluated. High-risk hot spots and BSI in the patients were evaluated using the VSBONE BSI (ver.1.1) analysis software for Tc-99m HMDP that scanned SPECT/CT and automatically defined the data. The two groups were compared using the Pearson chi-square test and Mann-Whitney U test for high-risk hot spots and BSI, respectively. A P value of <0.05 was considered statistically significant. High-risk hot spot occurrence was significantly correlated to bone metastases [sensitivity, 21/24 (87.5%); specificity, 40/73 (54.8%); accuracy, 61/97 (62.9%); P < 0.001]. The number of high-risk hot spots was higher in patients with bone metastases (5.96 ± 10.30) than in those without (0.90 ± 1.50; P < 0.001). Furthermore, the BSI for patients with bone metastases (1.44 ± 2.18%) was significantly higher than for those without (0.22 ± 0.44%; P < 0.001). A computer program that assessed BSI for Tc-99m HMDP may be useful in the evaluation of patients with bone metastases using SPECT/CT.

Applying Pix2pix to Translate Hyperemia in Blood Pool Image into Corresponding Increased Bone Uptake in Delayed Image in Three-Phase Bone Scintigraphy.

Delayed images may not be acquired due to severe pain, drowsiness, or worsening vital signs while waiting after blood pool imaging in three-phase bone scintigraphy. If the hyperemia in the blood pool image contains information from which increased uptake on the delayed images can be inferred, the generative adversarial network (GAN) can generate the increased uptake from the hyperemia. We attempted to apply pix2pix, a type of conditional GAN, to transform hyperemia into increased bone uptake. We enrolled 1464 patients who underwent three-phase bone scintigraphy for inflammatory arthritis, osteomyelitis, complex regional pain syndrome (CRPS), cellulitis, and recent bone injury. Blood pool images were acquired 10min after intravenous injection of Tc-99m hydroxymethylene diphosphonate, and delayed bone images were obtained after 3h. The model was based on the open-source code of the pix2pix model with perceptual loss. Increased uptake in the delayed images generated by the model was evaluated using lesion-based analysis by a nuclear radiologist in areas consistent with hyperemia in the blood pool images. The model showed sensitivities of 77.8% and 87.5% for inflammatory arthritis and CRPS, respectively. In osteomyelitis and cellulitis, their sensitivities of about 44% were observed. However, in cases of recent bone injury, the sensitivity was only 6.3% in areas consistent with focal hyperemia. The model based on pix2pix generated increased uptake in delayed images matching the hyperemia in the blood pool image in inflammatory arthritis and CRPS.

99mTc Bone-Avid Tracer Cardiac Scintigraphy: Role in Noninvasive Diagnosis of Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is an overlooked cause of heart failure, with substantial morbidity and mortality. The emergence of several novel therapies has fueled the interest in early and accurate diagnosis of ATTR-CA so that potentially life-saving pharmacologic therapy can be administered in a timely manner. The most promising imaging modality and biomarker is SPECT imaging with technetium 99m (99mTc)-radiolabeled bone-seeking tracers, which have high specificity in the diagnosis of ATTR-CA, potentially obviating biopsy. In this article, the authors provide a focused review on the use of 99mTc pyrophosphate (PYP), 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), and hydroxymethylene diphosphonate (HMDP) for diagnosis of ATTR-CA, present a systematic approach to interpretation of the scans, and highlight several common pitfalls to illustrate important diagnostic principles for accurate interpretation of these images. The authors indicate when to use endomyocardial biopsy for the diagnosis of cardiac amyloidosis and conclude with a section on quantitation of 99mTc-PYP/DPD/HMDP imaging.

Comparison of maximum and mean standardized uptake values of jaw pathologies with bone SPECT/CT: an especial focus on medication-related osteonecrosis of the jaw.

To investigate the comparison of maximum and mean standardized uptake values (SUVs) of jaw pathologies with bone Single-photon emission computed tomography/computed tomography (SPECT/CT), and a special focus on medication-related osteonecrosis of the jaw (MRONJ). Eighty-nine patients with jaw pathologies (63 MRONJ, 13 chronic osteomyelitis, 11 osteoradionecrosis and 2 primary intraosseous carcinoma) underwent bone SPECT/CT scans acquisition at 4 h after intravenous injection of Tc-99m hydroxymethylene diphosphonate in this prospective study. The evaluation of mean and maximum SUVs of jaw pathologies were performed using Q. Metrix and Xeleris workstation and defined the data automatically. Statistical analyses were performed by Pearson's correlation coefficient for comparison of maximum and mean SUVs and Mann-Whitney U-test for SUVs of MRONJ. A P value lower than 0.05 was considered to indicate statistical significance. Maximum SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 17.6 ± 8.4, 21.7 ± 7.1, 11.9 ± 4.8 and 26.6 ± 7.0, respectively. Mean SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 10.1 ± 4.9, 11.9 ± 3.3, 7.0 ± 2.8 and 10.1 ± 4.5, respectively. The maximum SUV of jaw pathologies was significantly correlated with the mean SUV (Y = 0.494X + 1.228; R2 = 0.786; P < 0.001). Furthermore, maximum and mean SUVs of MRONJ had significant differences in underlying diseases, medication and staging. The maximum and mean SUVs with bone SPECT/CT can be an effective tool for the quantitative evaluation of jaw pathologies, especially MRONJ.

Clinical Usefulness of SPECT/CT for Assessing Postoperative Outcomes After Medial Opening-Wedge High Tibial Osteotomy.

Background:Qualitative studies have explored changes in Tc-99m hydroxymethylene diphosphonate (HDP) uptake on single-photon emission computed tomography and computed tomography (SPECT/CT) as a result of offloading after medial opening-wedge high tibial osteotomy (MOWHTO) in patients with medial compartment knee osteoarthritis. However, whether changes in the Tc-99m HDP uptake on SPECT/CT reflect the degree of clinical improvement in postoperative outcomes, especially when using minimal clinically important differences (MCIDs), has not been investigated.Purpose:To investigate the association between changes in Tc-99m HDP uptake on SPECT/CT and MCID-based improvement on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score in patients who underwent MOWHTO.Study Design:Cross-sectional study; Level of evidence, 3.Methods:The study included 35 knees in 31 patients who underwent MOWHTO. SPECT/CT was performed preoperatively and 3 years postoperatively with clinical and radiological assessments. On SPECT/CT, the knee joint was divided into 10 regions, and the radiotracer uptake amount of each region was divided by the uptake amount of the reference zone. Patients were divided into 2 groups based on whether they achieved the MCID of 16.1 points on the WOMAC at 3 years postoperatively, and changes in uptake amount on SPECT/CT were compared between the groups.Results:At 3 years postoperatively, 22 patients achieved the MCID on the WOMAC (62.9%; above-MCID group) and 13 patients did not (37.1%; below-MCID group). In the above-MCID group, significant improvement was observed in the WOMAC after MOWHTO (from 55.8 to 19.6; P < .05); however, significant improvement was not observed in the below-MCID group (from 38.8 to 32.3; P = .100). Based on mean change of uptake on SPECT/CT in each region, the above-MCID group showed significantly greater reduction of uptake on SPECT/CT than the below-MCID group in the femoral anteromedial compartment (P = .004), tibial anteromedial compartment (P = .009), and tibial anterolateral compartment (P = .031).Conclusion:Reduction in radiotracer uptake on SPECT/CT of the knee joint reflected clinical improvement in patient-reported outcomes following MOWHTO.

Comparison of skeletal segmentation by deep learning-based and atlas-based segmentation in prostate cancer patients.

We aimed to compare the deep learning-based (VSBONE BSI) and atlas-based (BONENAVI) segmentation accuracy that have been developed to measure the bone scan index based on skeletal segmentation. We retrospectively conducted bone scans for 383 patients with prostate cancer. These patients were divided into two groups: 208 patients were injected with 99mTc-hydroxymethylene diphosphonate processed by VSBONE BSI, and 175 patients were injected with 99mTc-methylene diphosphonate processed by BONENAVI. Three observers classified the skeletal segmentations as either a "Match" or "Mismatch" in the following regions: the skull, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, pelvis, sacrum, humerus, rib, sternum, clavicle, scapula, and femur. Segmentation error was defined if two or more observers selected "Mismatch" in the same region. We calculated the segmentation error rate according to each administration group and evaluated the presence of hot spots suspected bone metastases in "Mismatch" regions. Multivariate logistic regression analysis was used to determine the association between segmentation error and variables like age, uptake time, total counts, extent of disease, and gamma cameras. The regions of "Mismatch" were more common in the long tube bones for VSBONE BSI and in the pelvis and axial skeletons for BONENAVI. Segmentation error was observed in 49 cases (23.6%) with VSBONE BSI and 58 cases (33.1%) with BONENAVI. VSBONE BSI tended that "Mismatch" regions contained hot spots suspected of bone metastases in patients with multiple bone metastases and showed that patients with higher extent of disease (odds ratio = 8.34) were associated with segmentation error in multivariate logistic regression analysis. VSBONE BSI has a potential to be higher segmentation accuracy compared with BONENAVI. However, the segmentation error in VSBONE BSI occurred dependent on bone metastases burden. We need to be careful when evaluating multiple bone metastases using VSBONE BSI.

Radiopharmaceutical Supply Disruptions and the Use of 99mTc-Hydroxymethylene Diphosphonate as an Alternative to 99mTc-Pyrophosphate for the Diagnosis of Transthyretin Cardiac Amyloidosis: An ASNC Information Statement

Radiopharmaceutical Supply Disruptions and the Use of 99mTc-Hydroxymethylene Diphosphonate as an Alternative to 99mTc-Pyrophosphate for the Diagnosis of Transthyretin Cardiac Amyloidosis: An ASNC Information Statement

Diagnosis of prosthetic joint infection at the hip using the standard uptake value of three-phase 99mTc-hydroxymethylene diphosphonate SPECT/CT.

To retrospectively investigate whether the standard uptake value (SUV) of 99mTc-bone single-photon emission computed tomography (SPECT)/CT could be useful for predicting prosthetic joint infection (PJI) at the hip. We analyzed the cases of 37 patients with a suspected PJI at the hip who underwent 99mTc-bone SPECT/CT and surgical intervention with pathological and bacterial examinations. We divided the cases into those with and those without a causative bacterium detected in a surgical specimen, i.e., the positive bacterial culture (PBC) group (n = 17) and negative bacterial culture (NBC) group (n = 20). Cases with neutrophilic infiltration of surgical specimen comprised the positive neutrophilic infiltration (PINF) group (n = 18) and those without INF comprised the non-neutrophilic infiltration (NINF) group (n = 19). Quantitative analyses were performed using maximum SUVs and peak SUVs of blood-pool (BP) phase images (SUVmaxBP and SUVpeakBP) and late (LT)-phase images (SUVmaxLT and SUVpeakLT). Regarding the bacterial cultures, there were significant differences between the PBC and NBC groups in SUVmaxBP (5.26 ± 1.49 vs. 4.21 ± 1.15, respectively; p = 0.019), SUVpeakBP (4.89 ± 1.32 vs. 3.87 ± 1.06, p = 0.012), SUVmaxLT (16.10 ± 6.36 vs. 11.67 ± 4.95, p = 0.026), and SUVpeakLT (14.58 ± 5.83 vs. 10.49 ± 4.31 p = 0.036). Regarding neutrophilic infiltration, there were significant differences between the PINF and NINF groups in SUVmaxBP (5.18 ± 1.48 vs. 4.24 ± 1.19, p = 0.047) and SUVpeakBP (4.78 ± 1.32 vs. 3.92 ± 1.10, p = 0.043). An SUV analysis of 99mTc-bone SPECT/CT is a useful method to differentiate a PJI at the hip from non-infection.

Volumetric analysis of mandibular lesions with SPECT/CT: a pilot clinical study of maximum standardized uptake value.

PurposeThis study was designed to investigate mandibular lesions using volumetric analysis with bone single-photon emission computed tomography/computed tomography (SPECT/CT).Material and methodsEight patients with mandibular lesions underwent SPECT/CT scan acquisition 4 hours after injection of Tc-99m hydroxymethylene diphosphonate (HMDP). Regarding volumetric analysis, maximum standar-dized uptake value (SUV) was obtained using software and a workstation (Q.Volumetrix MI and GEniE-Xeleris 4 DR, respectively). The localization and size of the volume of interest (VOI) can be drawn over the lesion, mesial, distal, and opposite side as normal using the CT, SPECT, and SPECT/CT transaxials, coronals, and sagittals as the anatomical reference. Q.Volumetrix MI can analyse SUV of lesions by organ segmentation using optional pan and zoom imaging. Then, the dosimetry software provided multiple quantitative data for a given VOI. Statistical analyses for the maximum SUV were performed by Mann-Whitney U test. A p-value lower than 0.05 was considered as statistically significant.ResultsMaximum SUVs for medication-related osteonecrosis of the jaw (n = 4, 25.4 ± 4.9), chronic osteomyelitis (n = 3, 14.6 ± 3.1), and squamous cell carcinoma (n = 1, 31.7) were significantly higher than those of the opposite side as normal mandible (3.8 ± 0.7, 4.6 ± 1.8, and 7.4, respectively; p = 0.000).ConclusionsVolumetric analysis with SPECT/CT could be useful for the evaluation of mandibular lesions, such as detecting and surgical planning.

Frequent, quantitative bone planar scintigraphy for determination of bone anabolism in growing mice.

BackgroundTo provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route.MethodsRepeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights.ResultsA total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 6 to 15.0 ± 3.3 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of −0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24.ConclusionThis methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.

An alternative method for radioactivity measurement in quantitative bone SPECT/CT imaging.

Bone scintigraphy with combined single-photon emission computed tomography (SPECT) and computed tomography (CT) has become widely used for the detection of bone metastases. However, calculation of the semi-quantitative standardized uptake value (SUV) requires measurement of the pre- and post-injection radioactivity of the radiopharmaceutical. This study aimed to compare measured and fixed input radioactivity values for quantitative SPECT/CT bone imaging to examine whether the fixed measurement method of radiopharmaceutical radioactivity could be used as an alternative method. Four different methods were used to quantify the Tc-99m hydroxymethylene diphosphonate input radioactivity: (A) measured pre- and post-injection radioactivity values; (B) measured pre-injection and fixed post-injection radioactivity values; (C) fixed pre-injection and measured post-injection radioactivity values; (D) fixed pre- and post-injection radioactivity values. All SPECT/CT acquisitions were analyzed using bone SPECT analysis software, and the semi-quantitative parameters (SUVpeak and SUVmean) were recorded and compared for each analytical method. Two semi-quantitative parameters showed significant differences between analytical methods A and B, A and D, and C and D. However, an additional subgroup analysis performed on patients whose median post-injection measured radioactivity value was <1.5 MBq showed no significant differences in parameters between all analytical methods. Measurement of the radiopharmaceutical radioactivity can be an alternative method because it reduces the volume of radioactivity post-injection. The simplified fixed measurement method of radiopharmaceutical radioactivity can be used as an alternative method in cases when measuring the radioactivity in quantitative bone SPECT/CT imaging is missed.

Quantitative bone single-photon emission computed tomography imaging for uninfected nonunion: comparison of hypertrophic nonunion and non-hypertrophic nonunion

BackgroundRecently, a standardized uptake value (SUV) has been used to evaluate bone single-photon emission computed tomography (SPECT). The aim of this study was to investigate quantitative SPECT imaging of uninfected nonunion to compare hypertrophic nonunion and non-hypertrophic nonunion using volume-based parameters.MethodsWe evaluated 23 patients with uninfected nonunion who underwent SPECT acquisition 3 h after an injection of 99mTc-hydroxymethylene diphosphonate or 99mTc-methylene diphosphonate from April 2014 to November 2019. We reconstructed the acquired data and performed voxel-based quantitative analysis using the GI-BONE software. Quantitative parameters, maximum SUV (SUVmax), peak SUV (SUVpeak), and mean SUV (SUVmean) in the high and low uptake areas of nonunion were compared between hypertrophic nonunion and non-hypertrophic nonunion. The contralateral limb was used as a control, and the ratios of the quantitative parameters were calculated.ResultsThe values for the quantitative parameters (high uptake area/low uptake area, respectively), SUVmax control ratio (12.13 ± 4.95/6.44 ± 4.71), SUVpeak control ratio (11.65 ± 4.58/6.45 ± 4.64), and SUVmean control ratio (11.94 ± 5.03/6.28 ± 4.95) for hypertrophic nonunion were higher than those for non-hypertrophic nonunion (7.82 ± 4.76/3.41 ± 2.09 (p = 0.065/0.12), 7.56 ± 4.51/3.61 ± 2.23 (p = 0.065/0.22), and 7.59 ± 5.18/3.05 ± 1.91 (p = 0.076/0.23)).ConclusionsSUVmax, SUVpeak, and SUVmean control ratios obtained from bone SPECT images can quantitatively evaluate the biological activity of nonunions and may be an effective evaluation method for treatment decisions, especially the necessity of autologous bone grafting.

Effect of Ursodeoxycholic Acid on the Biodistribution and Excretion of Technetium-99m Radiopharmaceuticals in Rat: A Potential Image Quality Enhancer.

PurposeThis study aimed to investigate the effect of ursodeoxycholic acid (UDCA) on the biodistribution and excretion of technetium-99m (Tc-99m)-labeled radiopharmaceuticals.Materials and MethodsTc-99m hydroxy-methylene-diphosphonate (HDP), Tc-99m pertechnetate, and Tc-99m dimercaptosuccinic acid (DMSA) were injected via the tail vein of rats. After 30 min, the control group was administered saline, and the UDCA group was given UDCA orally. Scintigraphy images were acquired after 30 min and 1, 2, 3, and 4 h. Radioactivity and rate of change were compared. Tc-99m mercaptoacetyltriglycine (MAG3) imaging was also performed.ResultsIn image analysis of Tc-99m HDP, radioactivity of the buttock was lower in the UDCA group at 4 h. Rates of change in the buttock were significantly different at 3 h–30 min and 4 h–30 min, and buttock radioactivity in the UDCA group had decreased more. In analysis of Tc-99m pertechnetate, radioactivity of the buttock was higher in the control group. Rates of change in the thyroid gland and buttock were different at 1 h–30 min, 3 h–30 min, and 4 h–30 min, with radioactivity in the UDCA group decreasing more. In the analysis of Tc-99m DMSA, while the radioactivity of the kidneys in the control group showed little decrease at 1 h–30 min, that in the UDCA group increased. In the analysis of Tc-99m MAG3 images, radioactivity and radioactivity/total body radioactivity (TBA) values for the kidneys were higher in the UDCA group at 2 min. At 5 and 10 min, radioactivity/TBA values for soft tissue in the UDCA group were lower than those in the control group.ConclusionThis study demonstrated that administration of UDCA increases renal excretion and soft tissue clearance of radiopharmaceuticals. This investigation could contribute to the broadening of applications of UDCA.