The effect of electro-anatomical mapping on the success rate and fluoroscopy time in supra-ventricular tachycardia ablation in children: single centre retrospective study.

AIMS: To evaluate the effect of electro-anatomical mapping on success rate and fluoroscopy time in ablation of supraventricular tachycardia substrates in a large group of children. METHODS: Patients referred from multiple centres in the Netherlands and who received a first ablation for supraventricular tachycardia substrates in the Leiden University Medical Center between 2014 and 2020 were included in this retrospective cohort study. They were divided in procedures in patients with fluoroscopy and procedures in patients using electro-anatomical mapping. RESULTS: Outcomes of ablation of 373 electro-anatomical substrates were analysed. Acute success rate in the fluoro-group (n = 170) was 95.9% compared to 94.5% in the electro-anatomical mapping group (n = 181) (p = 0.539); recurrence rate was 6.1% in the fluoro-group and 6.4% in the electro-anatomical mapping group (p = 0.911) after a 12-months follow-up. Redo-ablations were performed in 12 cases in the fluoro-group and 10 cases in the electro-anatomical mapping group, with a success rate of 83.3% versus 80.0%, resulting in an overall success rate of 95.9% in the fluoro-group and 92.8% in the electro-anatomical mapping group (p = 0.216) after 12 months. Fluoroscopy time and dose area product decreased significantly from 16.00 ± 17.75 minutes (median ± interquartile range) to 2.00 ± 3.00 minutes (p = 0.000) and 210.5 µGym2 ± 249.3 to 32.9 µGym2 ± 78.6 (p = 0.000), respectively. In the fluoro-group, four complications occurred (2.0%) and in the electro-anatomical mapping group no complications occurred. CONCLUSION: These results demonstrate that ablations of supraventricular tachycardia substrates in children remain a highly effective and safe treatment after the introduction of electro-anatomical mapping as a standard of care, while significantly reducing fluoroscopy time and dose area product.

Validation of a Monte Carlo simulated cardiac phantom for planar and SPECT studies.

PURPOSE: This work aimed to validate Monte Carlo (MC) simulated cardiac phantoms for the evaluation of planar- and SPECT-gated-blood-pool (GBP-P and GBP-S) studies. METHODS: A comparison of gamma camera system performance criteria measurements (energy resolution, spatial resolution, sensitivity) with MC simulations was conducted. Furthermore, the accuracy of measured and simulated volumes of two stereolithography-printed cardiac phantoms (based on 4D-XCAT phantoms) was assessed. Finally, the simulated GBP-P and GBP-S XCAT studies were validated by comparing calculated left ventricular ejection fraction (LVEF) and ventricle volume values with known parameters. RESULTS: The simulated performance criteria compared well with measured values (energy resolution difference: 0.1 ± 0.10%; spatial resolution (full width at half maximum) difference ≤ 0.5 ± 0.8 mm and system sensitivity difference ≤ 6.2 ± 0.62cps/MBq). The measured and simulated cardiac phantoms were in good agreement; the left anterior oblique views compared well. This is supported by line profiles through these phantoms and on average, simulated counts were 5.8% lower than measured counts. The LVEF values calculated from the GBP-P and GBP-S simulated data differ from known values (2.8 ± 0.64% and 0.8 ± 0.52%). The differences between the known XCAT LV volumes and simulated GBP-S calculated volumes were -1.2 ± 1.91 ml and -1.5 ± 0.96 ml for the end-diastolic and end-systolic volumes. CONCLUSION: The MC-simulated cardiac phantom has been validated successfully. Stereolithography-printing allows researchers to create clinically realistic organ phantoms and is a valuable tool for validating MC simulations and clinical software. By conducting GBP simulation studies with various XCAT models, the user will be able to generate GBP-P and GBP-S databases for future software evaluation.

Validation of Monte Carlo-based calculations for megavolt electron beams for IORT and FLASH-IORT.

In Intra-Operative Radiation Therapy (IORT) the tumour site is surgically exposed and normal tissue located around the tumour may be avoided. Electron applicators would require large surgical incisions; therefore, the preferred mechanism for beam collimation is the IORT cone system. FLASH radiotherapy (FLASH-RT) involves the treatment of tumours at ultra-high dose rates and the IORT cone system can also be used. This study validates the Monte Carlo-based calculations for these small electron beams to accurately determine the dose characteristics of each possible cone-energy combination as well as custom-built alloy cutouts attached to the end of the IORT cone. This will contribute to accurate dose distribution and output factor calculations that are essential to all radiation therapy treatments. A Monte Carlo (MC) model was modelled for electron beams produced by a Siemens Primus LINAC and the IORT cones. The accelerator was built with the component modules available in the BEAMnrc code. The phase-space file generated by the BEAM simulation was used as the source input for the subsequent DOSXYZnrc simulations. Percentage Depth Dose (PDD) data and profiles were extracted from the dose distributions obtained with the DOSXYZnrc simulations. These beam characteristics were compared with measured data for 6, 12, and 18 MeV electron beams for the IORT open cones of diameters 19, 45, and 64 mm and irregularly shaped cutouts. The MC simulations could replicate electron beams within a criterion of 3%/3 mm. Applicator factors were within 0.7%, and cone factors showed good agreement, except for the 9 mm cone size. Based on the successful comparisons between measurement and MC-calculated dose distributions, output factors for the open cones and for small irregularly shaped IORT beams, it may be concluded that the Monte Carlo based dose calculation could replicate electron beams used for IORT and FLASH-IORT.

Measured, calculated, and egs_brachy I-125 dose distributions in a gold plaque for retinoblastoma treatment.

BACKGROUND: This study measured and calculated dose distributions around a unique gold plaque for whole-eye radiotherapy (to treat retinoblastoma). The applicator consists of a pericorneal ring attached to the four extraocular muscles and four legs, each loaded with I-125 seeds. They are inserted beneath the conjunctiva in-between each pair of muscles and attached anteriorly to the ring. The applicator was designed in such a way that the dose is directed toward the middle of the eye while sparing surrounding tissues. PURPOSE: (I) To compare the measured and calculated data obtained by thermoluminescent dosimeters (TLDs) in a solid-water phantom, a Gafchromic film in a solid-water phantom, the treatment planning systems, and Monte Carlo simulations; (II) to use Monte Carlo simulations for the determination of the dose to the organs at risk by taking the gold shielding and the anisotropy into account. METHODS: The dose around the applicator was measured using TLDs and Gafchromic EBT2 film in eye-shaped solid-water phantoms. Dose calculations were performed with the TheraPlan Plus and BrachyVision planning system and Monte Carlo simulations with egs_brachy code. A computer-aided design drawing of the applicator was created and used to create the input file for the Monte Carlo simulations. RESULTS: Monte Carlo calculated dose to the optic nerve is 64.8% of the central dose in the eye, whereas the planned dose is 93.7%. The Monte Carlo lens dose varies from 72.0% to 86.1%, whereas the planned dose varies from 73.0% to 84.3%. Monte Carlo-calculated dose to the bony orbit is 11.3%, whereas the planned dose is as high as 54.7% compared to the dose in the center region of the eye. CONCLUSIONS: The measured and Monte Carlo-simulated dose distributions matched well, whereas planned dose distributions showed discrepancies in some areas of the eye and outside of the eye due to their ignorance of the shielding effects of the plaque.

Characterization of Gafchromic™ film response against radionuclide activity.

PURPOSE: In this study, we used Gafchromic™ film XR-QA2 and RT-QA2 to characterize the film energy response against various radionuclides. We introduce a neutron depletion theoretical model that can describe film response as a function of cumulated activity. The film response was investigated with respect to different backscatter media such as polystyrene, perspex, lead and corrugated fibreboard carton (CFC). The sensitivity of the two types of film to different energies was also studied. Lastly, a film stack method was tested to allow the user to obtain sequential, cumulative doses at different time points. METHODS: Pieces of Gafchromic™ film XR-QA2 and RT-QA2 were exposed to Am-241, Cs-137, Tc-99m, and I-131 to obtain various cumulative activities. After 24 h, each film piece was digitized by scanning it with an Epson Perfection V330 flatbed scanner to obtain 48-bit RGB TIFF images. Afterwards, each image was processed with the Image J software package. The film response was fitted to a theoretically derived function based on the neutron depletion model and the Beer-Lambert Law and compared with an existing fitting function. Layers of the film were also placed together and irradiated with the above-mentioned radionuclides to investigate the possibility of increasing the sensitivity of the film as a dosimeter. The energy response of the two types of film was investigated by irradiating pieces of film with different photon energies. RESULTS: The theoretical response model fits OD vs cumulative activity accurately. XR-QA2 film shows good energy film response by using CFC as a backscatter material when using radionuclides. From the results, it is also evident that XR-QA2 is more sensitive to low energy gamma rays than RT-QA2. Its OD sensitivity can be increased by 2 ± 0.2 when using a double layer film and by 2.8 ± 0.3 when using a triple-layer film. By using a film stack, the experimental time can be decreased by using the second-order polynomial relationship obtained to relate the stacked film data to the single film data. CONCLUSIONS: The neutron depletion theoretical model is accurate and contains less free parameters than higher-order polynomial fits. The Gafchromic™ XR-QA2 film is also better to use in nuclear medicine because of its higher sensitivity. The sensitivity of the film as a dosimeter can also be increased by using multiple layers of film. Experiment times can also be decreased by using the film stack method.

External beam patient dose verification based on the integral quality monitor (IQM®) output signals.

BACKGROUND: The Integral Quality Monitor (IQM®) can essentially measure the integral fluence through a segment and provide real-time information about the accuracy of radiation delivery based on comparisons of measured segment signals and pre-calculated reference values. However, the present IQM chamber cannot calculate the dose in the patient. AIM: This study aims to make use of IQM field output signals to calculate the number of monitor units (MUs) delivered through an arbitrary treatment field in order to convert Monte Carlo (MC)-generated dose distributions in a patient model into absolute dose. METHODS: XiO and Monaco treatment planning systems (TPSs) were used to define treatment beam portals for cervix and esophagus conformal radiotherapy as well as prostate intensity-modulated radiotherapy for the translation of patient and beam setup information from DICOM to DOSXYZnrc. The planned beams were simulated in a patient model built from actual patient CT images and each simulated integral field/segment was weighted with its MUs before summation to get the total dose in the plan. The segment beam weights (MUs) were calculated as the ratio of the open-field IQM measured signal and the calculated signal per MU extracted from chamber sensitivity maps. These are the actual MUs delivered not just MUs set. The beam weighting method was evaluated by comparing weighted MC doses with original planned doses using profile and isodose comparisons, dose difference maps, γ analysis and dose-volume histogram (DVH) data. RESULTS: γ pass rates of up to 98% were found, except for the esophagus plan where the γ pass rate was below 45%. DVH comparisons showed good agreement for most organs, with the largest differences observed in low-density lung. However, these discrepancies can result from differences in dose calculation algorithms or differences in MUs used for dose weighting planned by the TPS and MUs calculated using IQM field output signals. To test this, a 4-field box DOSXYZnrc MC simulation weighted with planned (XiO) MUs was compared with the same simulation weighted with IQM-based MUs. Dose differences of up to 5% were found on the isocentre slice. For XiO versus MC, up to 7% dose differences were found, indicating additional error due to limitations of XiO's superposition algorithm. Dose differences between MC Monaco and MC EGSnrc were less than 3%. CONCLUSIONS: The most valuable comparison was MC versus MC as it eliminated algorithm discrepancies and evaluated dose differences precisely according to beam weighting. For XiO TPS, care must be taken as dose differences may also arise due to limitations in XiO's planning software, not merely due to differences in MUs. Overall, the IQM was successfully used to compute beam dose weights to accurately reconstruct the patient dose using unweighted MC beams. Our technique can be used for pre-treatment QA provided each segment output is known and an accurate linac source model is available.

Integral quality monitor (IQM® ) signal correction factors for small fields to predict larger irregular segment output signals.

PURPOSE: To develop a method of correcting for the inaccuracies of small adjoined field segments in their contribution to larger fields in order to get a better match between their combined signals and the measured integral quality monitor (IQM) open field signals. This would enable the pre-calculation of known irregular segment output signals per monitor unit (MU), which would be later useful for patient-based dose calculations for treatment verification during pre-treatment treatment validation using the IQM output signal per MU. METHODS: Small fields exhibit source obscurity and loss of scatter, resulting in smaller signals being measured by the IQM and the subsequent underestimation of IQM output signals of larger segments obtained by combining small segment signals. Larger field segments were broken down into a set of smaller, regular, abutted segments, whose individual signals were added together to get the predicted output signal of the larger field. The signal/MU for each smaller constituent segment was extracted at its exact location from measured IQM response maps, generated by irradiating the IQM with small elementary segments ranging from 1 × 1 cm2 -5 × 5 cm2 , shifting each segment 1 cm at a time and measuring its corresponding output signal/MU throughout the entire IQM sensitive area. The predicted signal was weighed against the IQM-measured signal of the open field to calculate a signal correction factor (CF) of each elementary segment size. The CFs were applied to known signals of each set of elementary fields before summation in order to pre-calculate signals of larger irregular fields more accurately. The dependence of CFs on elementary segment size, location of the open field, and beam energy was investigated. RESULTS: CFs exhibited an exponential decrease with increase in elementary segment size. CFs were also invariant with beam energy, changing by ≤1% from 6-15 MV. Uncorrected signals for regular fields had relative errors of above 5% whilst signal correction reduced these errors down to ~0.4% (i.e., 99.6% accuracy). For irregular fields, signal correction reduced calculation errors from ~10% to well below 1.5%. Larger signal prediction errors were found when smaller segments were used to reconstruct the field. Open field size and location had a great impact on measured signals but virtually no significance on CFs. CONCLUSIONS: Results indicate that summation of small segment signals cannot sufficiently reproduce the same output given by an open field if individual elementary segment signals are not weighted with their respective CFs. This effect is particularly predominant for elementary segments 3 × 3 cm2 and for irregular fields. The method outlined enabled the calculation of signal CFs in order to match predicted signals with measured signals to 98.5% accuracy, thus enabling the pre-calculation of irregular segment output signals/MU for future patient dose calculations.

Dosimetry Effects Caused by Unilateral and Bilateral Hip Prostheses: A Monte Carlo Case Study in Megavoltage Photon Radiotherapy for Computed Tomography Data without Metal Artifacts.

BACKGROUND: Hip prostheses (HPs) are routinely used in hip augmentation to replace painful or dysfunctional hip joints. However, high-density and high-atomic-number (Z) inserts may cause dose perturbations in the target volume and interface regions. AIM: To evaluate the dosimetric influence of various HPs during megavoltage conformal radiotherapy (RT) of the prostate using Monte Carlo (MC) simulations. MATERIALS AND METHODS: BEAMnrc and DOSXYZnrc MC user-codes were respectively used to simulate the linac head and to calculate 3D absorbed dose distributions in a computed tomography (CT)-based phantom. A novel technique was used to synthetically introduce HPs into the raw patient CT dataset. The prosthesis materials evaluated were stainless steel (SS316L), titanium (Ti6Al4V), and ultra-high-molecular-weight polyethylene (UHMWPE). Four, five, and six conformal photon fields of 6-20 MV were used. RESULTS: The absorbed dose within and beyond metallic prostheses dropped significantly due to beam attenuation. For bilateral HPs, the target dose reduction ranged up to 23% and 17% for SS316L and Ti6Al4V, respectively. For unilateral HP, the respective dose reductions were 19% and 12%. Dose enhancement was always <1% for UHMWPE. The 6-field plan produced the best target coverage. Up to 38% dose increase was found at the bone-SS316L proximal interface. CONCLUSIONS: The novel technique used enabled the complete exclusion of metal artifacts in the CT dataset. High-energy plans with more oblique beams can help minimize dose attenuation through HPs. Shadowing and interface effects are density dependent and greatest for SS316L, while UHMWPE poses negligible dose perturbation.

Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy.

BACKGROUND: Cardiomyopathies are usually inherited and predominantly affect adults, but they can also present in childhood. Although our understanding of the molecular basis of pediatric cardiomyopathy has improved, the underlying mechanism remains elusive in a substantial proportion of cases. OBJECTIVES: This study aimed to identify new genes involved in pediatric cardiomyopathy. METHODS: The authors performed homozygosity mapping and whole-exome sequencing in 2 consanguineous families with idiopathic pediatric cardiomyopathy. Sixty unrelated patients with pediatric cardiomyopathy were subsequently screened for mutations in a candidate gene. First-degree relatives were submitted to cardiac screening and cascade genetic testing. Myocardial samples from 2 patients were processed for histological and immunohistochemical studies. RESULTS: We identified 5 patients from 3 unrelated families with pediatric cardiomyopathy caused by homozygous truncating mutations in ALPK3, a gene encoding a nuclear kinase that plays an essential role in early differentiation of cardiomyocytes. All patients with biallelic mutations presented with severe hypertrophic and/or dilated cardiomyopathy in utero, at birth, or in early childhood. Three patients died from heart failure within the first week of life. Moreover, 2 of 10 (20%) heterozygous family members showed hypertrophic cardiomyopathy with an atypical distribution of hypertrophy. Deficiency of alpha-kinase 3 has previously been associated with features of both hypertrophic and dilated cardiomyopathy in mice. Consistent with studies in knockout mice, we provide microscopic evidence for intercalated disc remodeling. CONCLUSIONS: Biallelic truncating mutations in the newly identified gene ALPK3 give rise to severe, early-onset cardiomyopathy in humans. Our findings highlight the importance of transcription factor pathways in the molecular mechanisms underlying human cardiomyopathies.

Cardiovascular imaging in pediatric patients using dual source CT.

Cardiovascular CT acquisition protocol optimization in pediatric patients, including newborns is often challenging. This might be due to non-cooperative patients, the complexity and variety of diseases and the need for stringent dose minimization. Motion artifacts caused by voluntary and involuntary motion are most frequently seen in cardiac imaging with high heart and respiratory rates. Dual source scanners of the second and third generation are particularly well suited to respond to these challenges. This can be accomplished with advanced scan options, such as high pitch scanning, short rotation times, automated tube voltage selection, tube current modulation and iterative reconstruction.

Bradyarrhythmias: first presentation of arrhythmogenic right ventricular cardiomyopathy?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder characterized by progressive replacement of myocardial cells by fibro-fatty tissue giving rise to ventricular tachyarrhythmias. In this case report, we describe a pediatric patient with sinoatrial arrests and second degree atrioventricular conduction block several years before ARVC became apparent. These findings suggest that bradyarrhythmias can also be the first expression of ARVC.

Phenotypic variability of atypical 22q11.2 deletions not including TBX1.

Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in humans. The TBX1 gene is considered to be the major candidate gene for the main features in 22q11.2 deletion syndrome, including congenital heart malformations, (para)thyroid hypoplasia, and craniofacial abnormalities. We report on eight patients with atypical deletions of chromosome 22q11.2. These deletions comprise the distal part of the common 22q11.2 deleted region but do not encompass the TBX1 gene. Ten similar patients with overlapping distal 22q11.2 deletions have been reported previously. The clinical features of these patients are described and compared to those found in the classic 22q11.2 deletion syndrome. We discuss the possible roles of a position effect or haploinsufficiency of distally located genes (e.g., CRKL) in the molecular pathogenesis of the 22q11.2 deletion syndrome.

Rapid method for intraoperative assessment of aortic coarctation using three-dimensional echocardiography.

AIMS: The availability of three-dimensional (3D) echography with its multiplanar review analysis software on board now allows detailed examination in assessing morphological details. We evaluated the feasibility of 3D echography in assessing intraoperative morphological details of aortic coarctation (CoA) and its repair. METHODS AND RESULTS: Nine consecutive children scheduled for surgery of CoA were intraoperatively evaluated. Intraoperative 3D data sets were taken and analysed online before resection of the coarctation, showing the cross-sectional area (CSA) of the proximal aorta, coarctation, and the distal descending aorta. After resection of the coarctation and extended end-to-end anastomosis, a 3D data set was recorded to analyse the CSA of the anastomosis. In nine out of nine consecutive procedures, intraoperative 3D echography permitted comprehensive viewing and measuring of CoA and its repair. In three out of nine surgical procedures, intraoperative 3D echography provided additional information to support surgical decision-making. CONCLUSION: Intraoperative 3D echography is a feasible non-invasive imaging modality for intraoperative assessment of CoA and its repair, which provides useful additional information.

Excision of the tricuspid valve in a baby with Candida endocarditis.

We report on the management of Candida endocarditis in a 5-month old infant. The orifice of the tricuspid valve was totally obstructed, and the tension apparatus of the valve destroyed. Excision of the valve led to severe failure of the right heart. The combined use of anti-failure treatment, and reduction of right ventricular afterload with oxygen, nitric oxide and sildenafil, proved successful.