Machine learning to predict environmental dose rates from a radionuclide therapy service - a proof of concept study.

The Ionising Radiation Regulations 2017 requires prior risk assessment calculations and regular environmental monitoring of radiation doses. However, the accuracy of prior risk assessments is limited by assumptions and monitoring only provides retrospective evaluation. This is particularly challenging in nuclear medicine for areas surrounding radionuclide therapy patient bathroom wastewater pipework. Machine learning (ML) is a technique that could be applied to patient booking records to predict environmental radiation dose rates in these areas to aid prospective risk assessment calculations, which this proof-of-concept work investigates. 540 days of a dosimeters historical daily average dose rate measurements and the corresponding period of department therapy booking records were used to train six different ML models. Predicted versus measured daily average dose rates for the following 60 days were analysed to assess and compare model performance. A wide range in prediction errors was observed across models. The gradient boosting regressor produced the best accuracy (root mean squared error = 1.10µSv.hr-1, mean absolute error = 0.87µSv.hr-1, mean absolute percentage error = 35% and maximum error = 3.26µSv.hr-1) and goodness of fit (R2= 0.411). Methods to improve model performance and other scenarios where this approach could prove more accurate were identified. This work demonstrates that ML can predict temporal fluctuations in environmental radiation dose rates in the areas surrounding radionuclide therapy wastewater pipework and indicates that it has the potential to play a role in improving legislative compliance, the accuracy of radiation safety and use of staff time and resources.

Acute abdominal surgical presentations in children.

Surgical conditions affecting the abdomen in children can be associated with significant morbidity and mortality if they are not recognised and managed appropriately. It is therefore important that the correct diagnosis is made quickly, and the appropriate intervention is initiated in a timely manner and, if necessary, rapid transfer is made to a specialist paediatric surgical facility. This article provides an overview of the different surgical presentations encountered in children, and outlines the most important points in the history, examination and management of such cases, whether encountered in the emergency setting or in the community. Two illustrative case studies have been included to demonstrate how these emergencies may present in clinical practice.

The role of serial 99mTc-DPD scintigraphy in monitoring cardiac transthyretin amyloidosis.

PURPOSE: Cardiac transthyretin amyloidosis is a usually fatal form of restrictive cardiomyopathy for which clinical trials of treatments are ongoing. It is anticipated that quantitative nuclear medicine scintigraphy, which is experiencing growing interest, will soon be used to evaluate treatment efficacy. We investigated its utility for monitoring changes in disease load over a significant time period. METHODS: Sixty-two treatment-naive patients underwent 99mTc-labelled 3,3-diphosphono-1,2propanodicarboxylic acid (99mTc-DPD) scintigraphy two to four times each over a five-year period. Quantitation of cardiac 99mTc-DPD retention was performed according to two established methods: measurement of heart-to-contralateral ratio (H/CL) in the anterior view (planar) and percentage of administered activity in the myocardium (SPECT). RESULTS: In total 170 datasets were analysed. Increased myocardial retention of 99mTc-DPD was demonstrable as early as 12 months from baseline. Year-on-year progression across the cohort was observed using SPECT-based quantitation, though on 30 occasions (27.8%) the change in our estimate was negative. CONCLUSIONS: The spread of our results was notably high compared to the year-on-year increases. If left unaccounted for, variance may draw fallacious conclusions about changes in disease load. We therefore urge caution in drawing conclusions solely from nuclear medicine scintigraphy on a patient-by-patient basis, particularly across a short time period.

Use of enzyme replacement therapy (Laronidase) before hematopoietic stem cell transplantation for mucopolysaccharidosis I: experience in 18 patients.

We describe the use of enzyme replacement therapy in conjunction with hematopoietic stem cell transplantation in 18 consecutive patients with severe mucopolysaccharidosis type I. The survival and engraftment rate was 89% overall and 93% for the 15 patients who received full-intensity conditioning.

Quantitation of 99mTc-DPD uptake in patients with transthyretin-related cardiac amyloidosis.

PURPOSE: Transthyretin (ATTR) amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), initially developed as a bone-seeking radiotracer, is remarkably sensitive for imaging cardiac ATTR amyloid deposits. Our aim was to investigate the feasibility and utility of estimating 99mTc-DPD uptake in myocardial tissue; this has the potential to yield reliable quantitative information on cardiac amyloid burden, which is urgently required to monitor disease progression and response to novel treatments. METHODS: Three methods of quantitation were developed and tested on 74 patients with proven cardiac ATTR amyloidosis who had recently undergone 99mTc-DPD planar whole-body imaging and SPECT-CT. Quantitative results were compared to measurements of extracellular volume fraction (ECV) by cardiac magnetic resonance imaging, a validated technique for measuring amyloid burden. RESULTS: An experienced clinician graded uptake using a widely-used visual scoring system as 1 (n = 15), 2 (n = 39) or 3 (n = 20). Linear correlations between the SPECT and ECV data (p < .001) were demonstrated. None of the methods showed that 99mTc-DPD uptake in the heart was significantly greater in patients with grade-3 uptake than in those with grade-2 uptake. CONCLUSIONS: Quantitation of 99mTc-DPD uptake in cardiac transthyretin amyloid deposits is complex and is hindered by competition for radiotracer with amyloid in skeletal muscle. The latter underlies differences in uptake between grade-2 and grade-3 patients, not cardiac uptake.

Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) amyloidosis and its relationship with skeletal muscle and soft tissue amyloid.

AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A-associated ATTRm (n = 59) amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001). CONCLUSION: 99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.

Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis.

AIMS: Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) is a sensitive method for imaging cardiac transthyretin (ATTR) amyloid. We report utility and limitations of (99m)Tc-DPD scintigraphy in 321 patients with suspected cardiac amyloidosis. METHODS AND RESULTS: The cohort included wild-type ATTR (ATTRwt) amyloidosis in 94 (29%), ATTR-Val122Ile amyloidosis in 38 (12%), hereditary ATTR (ATTRmt) amyloidosis in 46 (14%), primary light-chain (AL) amyloidosis in 44 (14%), secondary (AA) amyloidosis in three (1%), other hereditary amyloidosis types in nine (3%), undetermined types in two (0.5%), and 85 (26.5%) patients in whom systemic amyloidosis was ultimately excluded. All 158 patients with ATTR amyloidosis with clinical cardiac involvement had cardiac (99m)Tc-DPD uptake, with median Grade 2 intensity. Thirteen further ATTR amyloidosis patients without clinical evidence of cardiac involvement also demonstrated (99m)Tc-DPD cardiac uptake. Eighteen of 35 (51%) AL patients with cardiac involvement had (99m)Tc-DPD cardiac uptake (median Grade 1 intensity). SPECT imaging indicates that the apparent reciprocal reduction in bone uptake is due to masking of bone uptake by extensive soft-tissue uptake in ATTR amyloidosis, especially ATTRwt, and ATTR-Val122Ile types. CONCLUSION: (99m)Tc-DPD scintigraphy is a highly sensitive technique for imaging cardiac ATTR amyloidosis and is an important investigation in the diagnostic pathway of patients with cardiac amyloidosis. It is not specific for ATTR in isolation but must be interpreted in a broad clinical context to avoid dangerous diagnostic errors. Diffuse skeletal muscle uptake identifies muscle as a hitherto unrecognized site that merits investigation as a target organ in ATTR amyloidosis.