CT acquisition parameter selection in the real world: impacts on radiation dose and variation amongst 155 institutions.

OBJECTIVE: Quantify the relationship between CT acquisition parameters and radiation dose, how often parameters are adjusted in real-world practice, and their degree of contribution to real-world dose distribution. Identify discrepancies between parameters that are impactful in theory and impactful in practice. METHODS: This study analyses 1.3 million consecutive adult routine abdomen exams performed between November 2015 and Jan 2021 included in the University of California, San Francisco International CT Dose Registry of 155 institutions. We calculated geometric standard deviation (gSD) for five parameters (kV, mAs, spiral pitch, number of phases, scan length) to assess variation in practice. A Gaussian mixed regression model was performed to predict the radiation dose-length product (DLP) using the parameters. Three conceptualizations of "impact" were computed for each parameter. To reflect the theoretical impact, we predict the increase in DLP per 10% (and 15%) increase in the parameter. To reflect the real-world practical impact, we predict the increase in DLP per gSD increase in the parameter. RESULTS: Among studied examinations, mAs, number of phases, and scan length were frequently manipulated (gSD 1.52-1.70); kV was rarely manipulated (gSD 1.07). Theoretically, kV is the most impactful parameter (29% increase in DLP per 10% increase in kV, versus 5-9% increase for other parameters). In real-world practice, kV is less impactful; for each gSD increase in kV, the DLP increases by 20%, versus 22-69% for other parameters. CONCLUSION: Despite the potential impact of kV on radiation dose, this parameter is rarely manipulated in common practice and this potential remains untapped. CLINICAL RELEVANCE STATEMENT: CT beam energy (kV) modulation has the potential to strongly reduce radiation over-dosage to the patient, theoretically more so than similar degrees of modulation in other CT acquisition parameters. Despite this, beam energy modulation rarely occurs in practice, leaving its potential untapped. KEY POINTS: • The relationship between CT acquisition parameter selection and radiation dose roughly coincided with established theoretical understanding. • CT acquisition parameters differ from each other in frequency and magnitude of manipulation, with beam energy (kV) being rarely manipulated. • Beam energy (kV) has the potential to substantially impact radiation dose, but because it is rarely manipulated, it is the least impactful CT acquisition parameter affecting radiation dose in practice.

Dose length product to effective dose coefficients in adults.

OBJECTIVES: The most accurate method for estimating patient effective dose (a principal metric for tracking patient radiation exposure) from computed tomography (CT) requires time-intensive Monte Carlo simulation. A simpler method multiplies a scalar coefficient by the widely available scanner-reported dose length product (DLP) to estimate effective dose. We developed new adult effective dose coefficients using actual patient scans and assessed their agreement with Monte Carlo simulation. METHODS: A multicenter sample of 216,906 adult CT scans was prospectively assembled in 2015-2020 from the University of California San Francisco International CT Dose Registry and the University of Florida library of computational phantoms. We generated effective dose coefficients for eight body regions, stratified by patient sex, diameter, and scanner manufacturer. We applied the new coefficients to DLPs to calculate effective doses and assess their correlations with Monte Carlo radiation transport-generated effective dose. RESULTS: Effective dose coefficients varied by body region and decreased in magnitude with increasing patient diameter. Coefficients were approximately twofold higher for torso scans in smallest compared with largest diameter categories. For example, abdomen and pelvis coefficients decreased from 0.027 to 0.013 mSv/mGy-cm between the 16-20 cm and 41+ cm categories. There were modest but consistent differences by sex and manufacturer. Diameter-based coefficients used to estimate effective dose produced strong correlations with the reference standard (Pearson correlations 0.77-0.86). The reported conversion coefficients differ from previous studies, particularly in neck CT. CONCLUSIONS: New effective dose coefficients derived from empirical clinical scans can be used to easily estimate effective dose using scanner-reported DLP. CLINICAL RELEVANCE STATEMENT: Scalar coefficients multiplied by DLP offer a simple approximation to effective dose, a key radiation dose metric. New effective dose coefficients from this study strongly correlate with gold standard, Monte Carlo-generated effective dose, and differ somewhat from previous studies. KEY POINTS: • Previous effective dose coefficients were derived from theoretical models rather than real patient data. • The new coefficients (from a large registry/phantom library) differ from previous studies. • The new coefficients offer reasonably reliable values for estimating effective dose.

Large variation in radiation dose for routine abdomen CT: reasons for excess and easy tips for reduction.

OBJECTIVE: To characterize the use and impact of radiation dose reduction techniques in actual practice for routine abdomen CT. METHODS: We retrospectively analyzed consecutive routine abdomen CT scans in adults from a large dose registry, contributed by 95 hospitals and imaging facilities. Grouping exams into deciles by, first, patient size, and second, size-adjusted dose length product (DLP), we summarized dose and technical parameters and estimated which parameters contributed most to between-protocols dose variation. Lastly, we modeled the total population dose if all protocols with mean size-adjusted DLP above 433 or 645 mGy-cm were reduced to these thresholds. RESULTS: A total of 748,846 CTs were performed using 1033 unique protocols. When sorted by patient size, patients with larger abdominal diameters had increased dose and effective mAs (milliampere seconds), even after adjusting for patient size. When sorted by size-adjusted dose, patients in the highest versus the lowest decile in size-adjusted DLP received 6.4 times the average dose (1680 vs 265 mGy-cm) even though diameter was no different (312 vs 309 mm). Effective mAs was 2.1-fold higher, unadjusted CTDIvol 2.9-fold, and phase 2.5-fold for patients in the highest versus lowest size-adjusted DLP decile. There was virtually no change in kV (kilovolt). Automatic exposure control was widely used to modulate mAs, whereas kV modulation was rare. Phase was the strongest driver of between-protocols variation. Broad adoption of optimized protocols could result in total population dose reductions of 18.6-40%. CONCLUSION: There are large variations in radiation doses for routine abdomen CT unrelated to patient size. Modification of kV and single-phase scanning could result in substantial dose reduction. CLINICAL RELEVANCE: Radiation dose-optimization techniques for routine abdomen CT are routinely under-utilized leading to higher doses than needed. Greater modification of technical parameters and number of phases could result in substantial reduction in radiation exposure to patients. KEY POINTS: • Based on an analysis of 748,846 routine abdomen CT scans in adults, radiation doses varied tremendously across patients of the same size and optimization techniques were routinely under-utilized. • The difference in observed dose was due to variation in technical parameters and phase count. Automatic exposure control was commonly used to modify effective mAs, whereas kV was rarely adjusted for patient size. Routine abdomen CT should be performed using a single phase, yet multi-phase was common. • kV modulation by patient size and restriction to a single phase for routine abdomen indications could result in substantial reduction in radiation doses using well-established dose optimization approaches.

Sample size calculations for indirect standardization.

Indirect standardization, and its associated parameter the standardized incidence ratio, is a commonly-used tool in hospital profiling for comparing the incidence of negative outcomes between an index hospital and a larger population of reference hospitals, while adjusting for confounding covariates. In statistical inference of the standardized incidence ratio, traditional methods often assume the covariate distribution of the index hospital to be known. This assumption severely compromises one's ability to compute required sample sizes for high-powered indirect standardization, as in contexts where sample size calculation is desired, there are usually no means of knowing this distribution. This paper presents novel statistical methodology to perform sample size calculation for the standardized incidence ratio without knowing the covariate distribution of the index hospital and without collecting information from the index hospital to estimate this covariate distribution. We apply our methods to simulation studies and to real hospitals, to assess both its capabilities in a vacuum and in comparison to traditional assumptions of indirect standardization.

Dose length product to effective dose coefficients in children.

BACKGROUND: The most accurate method for estimating effective dose (the most widely understood metric for tracking patient radiation exposure) from computed tomography (CT) requires time-intensive Monte Carlo simulation. A simpler method multiplies a scalar coefficient by the widely available scanner-reported dose length product (DLP) to estimate effective dose. OBJECTIVE: Develop pediatric effective dose coefficients and assess their agreement with Monte Carlo simulation. MATERIALS AND METHODS: Multicenter, population-based sample of 128,397 pediatric diagnostic CT scans prospectively assembled in 2015-2020 from the University of California San Francisco International CT Dose Registry and the University of Florida library of highly realistic hybrid computational phantoms. We generated effective dose coefficients for seven body regions, stratified by patient age, diameter, and scanner manufacturer. We applied the new coefficients to DLPs to calculate effective doses and assessed their correlations with Monte Carlo radiation transport-generated effective doses. RESULTS: The reported effective dose coefficients, generally higher than previous studies, varied by body region and decreased in magnitude with increasing age. Coefficients were approximately 4 to 13-fold higher (across body regions) for patients <1 year old compared with patients 15-21 years old. For example, head CT (54% of scans) dose coefficients decreased from 0.039 to 0.003 mSv/mGy-cm in patients <1 year old vs. 15-21 years old. There were minimal differences by manufacturer. Using age-based conversion coefficients to estimate effective dose produced moderate to strong correlations with Monte Carlo results (Pearson correlations 0.52-0.80 across body regions). CONCLUSIONS: New pediatric effective dose coefficients update existing literature and can be used to easily estimate effective dose using scanner-reported DLP.

An Image Quality-informed Framework for CT Characterization.

Background Lack of standardization in CT protocol choice contributes to radiation dose variation. Purpose To create a framework to assess radiation doses within broad CT categories defined according to body region and clinical imaging indication and to cluster indications according to the dose required for sufficient image quality. Materials and Methods This was a retrospective study using Digital Imaging and Communications in Medicine metadata. CT examinations in adults from January 1, 2016 to December 31, 2019 from the University of California San Francisco International CT Dose Registry were grouped into 19 categories according to body region and required radiation dose levels. Five body regions had a single dose range (ie, extremities, neck, thoracolumbar spine, combined chest and abdomen, and combined thoracolumbar spine). Five additional regions were subdivided according to dose. Head, chest, cardiac, and abdomen each had low, routine, and high dose categories; combined head and neck had routine and high dose categories. For each category, the median and 75th percentile (ie, diagnostic reference level [DRL]) were determined for dose-length product, and the variation in dose within categories versus across categories was calculated and compared using an analysis of variance. Relative median and DRL (95% CI) doses comparing high dose versus low dose categories were calculated. Results Among 4.5 million examinations, the median and DRL doses varied approximately 10 times between categories compared with between indications within categories. For head, chest, abdomen, and cardiac (3 266 546 examinations [72%]), the relative median doses were higher in examinations assigned to the high dose categories than in examinations assigned to the low dose categories, suggesting the assignment of indications to the broad categories is valid (head, 3.4-fold higher [95% CI: 3.4, 3.5]; chest, 9.6 [95% CI: 9.3, 10.0]; abdomen, 2.4 [95% CI: 2.4, 2.5]; and cardiac, 18.1 [95% CI: 17.7, 18.6]). Results were similar for DRL doses (all P < .001). Conclusion Broad categories based on image quality requirements are a suitable framework for simplifying radiation dose assessment, according to expected variation between and within categories. © RSNA, 2021 See also the editorial by Mahesh in this issue.

Diagnostic reference levels and median doses for common clinical indications of CT: findings from an international registry.

OB JECTIVES: The European Society of Radiology identified 10 common indications for computed tomography (CT) as part of the European Study on Clinical Diagnostic Reference Levels (DRLs, EUCLID), to help standardize radiation doses. The objective of this study is to generate DRLs and median doses for these indications using data from the UCSF CT International Dose Registry. METHODS: Standardized data on 3.7 million CTs in adults were collected between 2016 and 2019 from 161 institutions across seven countries (United States of America (US), Switzerland, Netherlands, Germany, UK, Israel, Japan). DRLs (75th percentile) and median doses for volumetric CT-dose index (CTDIvol) and dose-length product (DLP) were assessed for each EUCLID category (chronic sinusitis, stroke, cervical spine trauma, coronary calcium scoring, lung cancer, pulmonary embolism, coronary CT angiography, hepatocellular carcinoma (HCC), colic/abdominal pain, appendicitis), and US radiation doses were compared with European. RESULTS: The number of CT scans within EUCLID categories ranged from 8,933 (HCC) to over 1.2 million (stroke). There was greater variation in dose between categories than within categories (p < .001), and doses were significantly different between categories within anatomic areas. DRLs and median doses were assessed for all categories. DRLs were higher in the US for 9 of the 10 indications (except chronic sinusitis) than in Europe but with a significantly higher sample size in the US. CONCLUSIONS: DRLs for CTDIvol and DLP for EUCLID clinical indications from diverse organizations were established and can contribute to dose optimization. These values were usually significantly higher in the US than in Europe. KEY POINTS: • Registry data were used to create benchmarks for 10 common indications for CT identified by the European Society of Radiology. • Observed US radiation doses were higher than European for 9 of 10 indications (except chronic sinusitis). • The presented diagnostic reference levels and median doses highlight potentially unnecessary variation in radiation dose.

Reference phantom selection in pediatric computed tomography using data from a large, multicenter registry.

BACKGROUND: Radiation dose metrics vary by the calibration reference phantom used to report doses. By convention, 16-cm diameter cylindrical polymethyl-methacyrlate phantoms are used for head imaging and 32-cm diameter phantoms are used for body imaging in adults. Actual usage patterns in children remain under-documented. OBJECTIVE: This study uses the University of California San Francisco International CT Dose Registry to describe phantom selection in children by patient age, body region and scanner manufacturer, and the consequent impact on radiation doses. MATERIALS AND METHODS: For 106,837 pediatric computed tomography (CT) exams collected between Jan. 1, 2015, and Nov. 2, 2020, in children up to 17 years of age from 118 hospitals and imaging facilities, we describe reference phantom use patterns by body region, age and manufacturer, and median and 75th-percentile dose-length product (DLP) and volume CT dose index (CTDIvol) doses when using 16-cm vs. 32-cm phantoms. RESULTS: There was relatively consistent phantom selection by body region. Overall, 98.0% of brain and skull examinations referenced 16-cm phantoms, and 95.7% of chest, 94.4% of abdomen and 100% of cervical-spine examinations referenced 32-cm phantoms. Only GE deviated from this practice, reporting chest and abdomen scans using 16-cm phantoms with some frequency in children up to 10 years of age. DLP and CTDIvol values from 16-cm phantom-referenced scans were 2-3 times higher than 32-cm phantom-referenced scans. CONCLUSION: REFERENCE PHANTOM SELECTION IS HIGHLY CONSISTENT, WITH A SMALL BUT SIGNIFICANT NUMBER OF ABDOMEN AND CHEST SCANS (~5%) USING 16-CM PHANTOMS IN YOUNGER CHILDREN, WHICH PRODUCES DLP VALUES APPROXIMATELY TWICE AS HIGH AS EXAMS REFERENCED TO 32-CM PHANTOMS.

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection.

BACKGROUND: Developing a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells' proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection. METHODS: Using 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets. RESULTS: An exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature's negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell-mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature's negative predictive value was 90.6% and its positive predictive value was 77.8%. CONCLUSIONS: Our findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.

A Mimic of Ankylosing Spondylitis, Ochronosis: Case Report and Review of the Literature.

PURPOSE OF REVIEW: Ochronosis and alkaptonuria are manifestations of the same condition-a rare autosomal recessive disorder resulting from a constitutional lack of homogentisate 1,2-dioxygenase (HGD) with the consequent accumulation of homogentisic acid (HGA). In ochronosis, HGA undergoes autoxidation as well as enzymatic oxidation to form an ochronotic pigment that accumulates in cartilage and connective tissues. In the beginning, there is homogentisic aciduria and pigmentation of cartilages and other connective tissues. In later years, generalized osteoarthritis of the spine and large joints, termed ochronotic arthropathy, develops. RECENT FINDINGS: The diagnosis is confirmed by quantitative measurement of HGA in urine and mutation analysis of the HGD gene. One of the differential diagnoses for the skin findings is exogenous ochronosis, a limited hyperpigmentation of skin caused by some chemicals. As for the lumbar spine findings, there can be radiographic similarities with ankylosing spondylitis (AS) including reduced intervertebral disc spaces and loss of lumbar lordosis; however, ochronosis will spare the sacroiliac joint, and the lumbar spine will show dense, wafer-like disk calcification with a vacuum disc phenomenon and broad syndesmophytes. Here, we present a case of a patient with probable ochronosis that was treated many years as ankylosing spondylitis without response, and we provide a review of the current literature on ochronosis pathogenesis, diagnosis, and treatment.

In vivo evidence of glutamate toxicity in multiple sclerosis.

OBJECTIVE: There is increasing evidence that altered glutamate (Glu) homeostasis is involved in the pathophysiology of multiple sclerosis (MS). The aim of this study was to evaluate the in vivo effects of excess brain Glu on neuroaxonal integrity measured by N-acetylaspartate (NAA), brain volume, and clinical outcomes in a large, prospectively followed cohort of MS subjects. METHODS: We used multivoxel spectroscopy at 3T to longitudinally estimate Glu and NAA concentrations from large areas of normal-appearing white and gray matter (NAWM and GM) in MS patients (n = 343) with a mean follow-up time of 5 years. Using linear mixed-effects models, Glu was examined as a predictor of NAA decline, annualized percentage brain volume change, and evolution of clinical outcomes (Multiple Sclerosis Functional Composite [MSFC], Paced Auditory Serial Addition Test-3 [PASAT], and Expanded Disability Status Scale). Glu/NAA ratio was tested as a predictor of brain volume loss and clinical outcomes. RESULTS: Baseline Glu[NAWM] was predictive of accelerated longitudinal decline in NAA[GM] (-0.06mM change in NAA[GM] /yr for each unit increase in Glu; p = 0.004). The sustained elevation of Glu[NAWM] was predictive of a loss of 0.28mM/yr in NAA[NAWM] (p < 0.001) and 0.15mM/yr in NAA[GM] (p = 0.056). Each 10% increase in Glu/NAA[NAWM] was associated with a loss of 0.33% brain volume/yr (p = 0.001), 0.009 standard deviations/yr in MSFC z-score (p < 0.001), and 0.17 points/yr on the PASAT (p < 0.001). INTERPRETATION: These results indicate that higher Glu concentrations increase the rate of NAA decline, and higher Glu/NAA[NAWM] ratio increases the rate of decline of brain volume, MSFC, and PASAT. This provides evidence of a relationship between brain Glu and markers of disease progression in MS.

Barrels XXVII meeting report: Barrels in the monument city.

The 27th annual Barrels meeting highlighted the latest advances in this rapidly growing field. The Barrels meeting annually focuses on the role of the posterior medial thalamus in somatosensation, dendritic processing, and the cortical dynamics involved during touch perception. Speakers utilized diverse molecular, physiological, computational techniques to understand the development, sensory processing, and motor commands that are involved with the rodent mystacial vibrissae. The meeting was held Thursday, 13 November through Friday, 14 November 2014 on the Homewood campus of Johns Hopkins University, Baltimore, MD.

Exercises in Anatomy, Connectivity, and Morphology using Neuromorpho.org and the Allen Brain Atlas.

Laboratory instruction of neuroscience is often limited by the lack of physical resources and supplies (e.g., brains specimens, dissection kits, physiological equipment). Online databases can serve as supplements to material labs by providing professionally collected images of brain specimens and their underlying cellular populations with resolution and quality that is extremely difficult to access for strictly pedagogical purposes. We describe a method using two online databases, the Neuromorpho.org and the Allen Brain Atlas (ABA), that freely provide access to data from working brain scientists that can be modified for laboratory instruction/exercises. Neuromorpho.org is the first neuronal morphology database that provides qualitative and quantitative data from reconstructed cells analyzed in published scientific reports. The Neuromorpho.org database contains cross species and multiple neuronal phenotype datasets which allows for comparative examinations. The ABA provides modules that allow students to study the anatomy of the rodent brain, as well as observe the different cellular phenotypes that exist using histochemical labeling. Using these tools in conjunction, advanced students can ask questions about qualitative and quantitative neuronal morphology, then examine the distribution of the same cell types across the entire brain to gain a full appreciation of the magnitude of the brain's complexity.

An ocean full of BARRELS: Barrels XXVI meeting report.

The 26th annual Barrels meeting was convened on the campus of the University of California San Diego, not far from the shores of the Pacific Ocean. The meeting focused on three main themes: the structure and function of the thalamic reticular nucleus, the neurovasculature system and its role in brain metabolism, and the origins and functions of cortical GABAergic interneurons. In addition to the major themes, there were short talks, a data blitz, and a poster session which highlighted the diversity and quality of the research ongoing in the rodent whisker-to-barrel system.

Improving the Safety of Computed Tomography Through Automated Quality Measurement: A Radiologist Reader Study of Radiation Dose, Image Noise, and Image Quality.

OBJECTIVES: The Centers for Medicare and Medicaid Services funded the development of a computed tomography (CT) quality measure for use in pay-for-performance programs, which balances automated assessments of radiation dose with image quality to incentivize dose reduction without compromising the diagnostic utility of the tests. However, no existing quantitative method for assessing CT image quality has been validated against radiologists' image quality assessments on a large number of CT examinations. Thus to develop an automated measure of image quality, we tested the relationship between radiologists' subjective ratings of image quality with measurements of radiation dose and image noise. MATERIALS AND METHODS: Board-certified, posttraining, clinically active radiologists rated the image quality of 200 diagnostic CT examinations from a set of 734, representing 14 CT categories. Examinations with significant distractions, motion, or artifact were excluded. Radiologists rated diagnostic image quality as excellent, adequate, marginally acceptable, or poor; the latter 2 were considered unacceptable for rendering diagnoses. We quantified the relationship between ratings and image noise and radiation dose, by category, by analyzing the odds of an acceptable rating per standard deviation (SD) increase in noise or geometric SD (gSD) in dose. RESULTS: One hundred twenty-five radiologists contributed 24,800 ratings. Most (89%) were acceptable. The odds of an examination being rated acceptable statistically significantly increased per gSD increase in dose and decreased per SD increase in noise for most categories, including routine dose head, chest, and abdomen-pelvis, which together comprise 60% of examinations performed in routine practice. For routine dose abdomen-pelvis, the most common category, each gSD increase in dose raised the odds of an acceptable rating (2.33; 95% confidence interval, 1.98-3.24), whereas each SD increase in noise decreased the odds (0.90; 0.79-0.99). For only 2 CT categories, high-dose head and neck/cervical spine, neither dose nor noise was associated with ratings. CONCLUSIONS: Radiation dose and image noise correlate with radiologists' image quality assessments for most CT categories, making them suitable as automated metrics in quality programs incentivizing reduction of excessive radiation doses.

A missense SNP in the tumor suppressor SETD2 reduces H3K36me3 and mitotic spindle integrity in Drosophila.

Mutations in SETD2 are among the most prevalent drivers of renal cell carcinoma (RCC). We identified a novel single nucleotide polymorphism (SNP) in SETD2, E902Q, within a subset of RCC patients, which manifests as both an inherited or tumor-associated somatic mutation. To determine if the SNP is biologically functional, we used CRISPR-based genome editing to generate the orthologous mutation within the Drosophila melanogaster Set2 gene. In Drosophila, the homologous amino acid substitution, E741Q, reduces H3K36me3 levels comparable to Set2 knockdown, and this loss is rescued by reintroduction of a wild-type Set2 transgene. We similarly uncovered significant defects in spindle morphogenesis, consistent with the established role of SETD2 in methylating α-Tubulin during mitosis to regulate microtubule dynamics and maintain genome stability. These data indicate the Set2 E741Q SNP affects both histone methylation and spindle integrity. Moreover, this work further suggests the SETD2 E902Q SNP may hold clinical relevance.

Associated radiation exposure from medical imaging and excess lifetime risk of developing cancer in pediatric patients with pulmonary hypertension.

Pediatric patients with pulmonary hypertension (PH) receive imaging studies that use ionizing radiation (radiation) such as computed tomography (CT) and cardiac catheterization to guide clinical care. Radiation exposure is associated with increased cancer risk. It is unknown how much radiation pediatric PH patients receive. The objective of this study is to quantify radiation received from imaging and compute associated lifetime cancer risks for pediatric patients with PH. Electronic health records between 2012 and 2022 were reviewed and radiation dose data were extracted. Organ doses were estimated using Monte Carlo modeling. Cancer risks for each patient were calculated from accumulated exposures using National Cancer Institute tools. Two hundred and forty-nine patients with PH comprised the study cohort; 97% of patients had pulmonary arterial hypertension, PH due to left heart disease, or PH due to chronic lung disease. Mean age at the time of the first imaging study was 2.5 years (standard deviation [SD] = 4.9 years). Patients underwent a mean of 12 studies per patient per year, SD = 32. Most (90%) exams were done in children <5 years of age. Radiation from CT and cardiac catheterization accounted for 88% of the total radiation dose received. Cumulative mean effective dose was 19 mSv per patient (SD = 30). Radiation dose exposure resulted in a mean increased estimated lifetime cancer risk of 7.6% (90% uncertainty interval 3.0%-14.2%) in females and 2.8% (1.2%-5.3%) in males. Careful consideration for the need of radiation-based imaging studies is warranted, especially in the youngest of children.