Measurement of potassium in rats using an In vivo neutron activation analysis system.

Abnormal levels of potassium are linked to several health conditions, including high blood pressure, cardiac dysfunction, kidney damage, and osteoporosis. Given the limited availability of in vivo measurement techniques, there is a need for novel methods to measure potassium to enhance the diagnosis and management of potassium metabolism related diseases. This study aimed to evaluate the feasibility of compact neutron generator based in vivo measurement system for quantification of potassium using rat carcasses. A cohort of thirty-nine rats (n = 20 males and 19 females, average weight 255 ± 15 and 163 ± 7 g) were sacrificed, and their carcasses were placed in polyethylene bottles. The rats were then positioned and irradiated in a carefully designed irradiation cave built alongside the neutron generator with an optimized thermal neutron flux and radiation dose ratio. The irradiation time was 10 min, followed by a 5-min decay and 2-h measurement using a high efficiency high purity germanium detector(HPGe). RESULTS: The average potassium concentration in male and female rats was found to be comparable (male 2874 ± 161 and female 2866 ± 144 µg/g). A marginally positive correlation between potassium concentration and weight was found in female rats only (male(20) = 0.07, P = 0.76 and female r(19) = 0.34, P = 0.15). We assessed the influence of manganese toxicity on potassium levels and observed no significant impact. These results were consistent with our previous study in mice. CONCLUSION: This study suggests that in vivo neutron activation analysis could serve as a promising method to quantify potassium and to investigate the storage and metabolism of potassium in human and in animals.

A machine learning approach for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma undergoing tomotherapy.

The purpose of this study was to establish an integrated predictive model that combines clinical features, DVH, radiomics, and dosiomics features to predict RIHT in patients receiving tomotherapy for nasopharyngeal carcinoma. Data from 219 patients with nasopharyngeal carcinoma were randomly divided into a training cohort (n = 175) and a test cohort (n = 44) in an 8:2 ratio. RIHT is defined as serum thyroid-stimulating hormone (TSH) greater than 5.6 µU/mL, with or without a decrease in free thyroxine (FT4). Clinical features, 27 DVH features, 107 radiomics features and 107 dosiomics features were extracted for each case and included in the model construction. The least absolute shrinkage and selection operator (LASSO) regression method was used to select the most relevant features. The eXtreme Gradient Boosting (XGBoost) was then employed to train separate models using the selected features from clinical, DVH, radiomics and dosiomics data. Finally, a combined model incorporating all features was developed. The models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. In the test cohort, the area under the receiver operating characteristic curve (AUC) for the clinical, DVH, radiomics, dosiomics and combined models were 0.798 (95% confidence interval [CI], 0.656-0.941), 0.673 (0.512-0.834), 0.714 (0.555-0.873), 0.698 (0.530-0.848) and 0.842 (0.724-0.960), respectively. The combined model exhibited higher AUC values compared to other models. The decision curve analysis demonstrated that the combined model had superior clinical utility within the threshold probability range of 1% to 79% when compared to the other models. This study has successfully developed a predictive model that combines multiple features. The performance of the combined model is superior to that of single-feature models, allowing for early prediction of RIHT in patients with nasopharyngeal carcinoma after tomotherapy.

Rodent hair is a Poor biomarker for internal manganese exposure.

Hair is used as a biomarker of manganese (Mn) exposure, yet there is limited evidence to support its utility to quantify internal vs external Mn exposure. C57BL/6 J mice and Sprague-Dawley rats were exposed in two blocks of 3 subcutaneous injections every 3 days starting on day 0 or 20. The control group received two blocks of saline (vehicle); Treatment A received the first block as Mn (50 mg/kg MnCl2 tetrahydrate), with the second block as either methylmercury (MeHg at 2.6 or 1.3 mg/kg) for mice or vehicle for rats; and Treatment B received Mn for both blocks. Hair was collected on days 0 and 60 from all treatment groups and Mn quantified by inductively coupled plasma-mass spectrometry (ICP-MS) and total Hg by Direct Mercury Analyzer (DMA). No correlation between internal Mn dose and hair Mn was observed, whereas hair Hg was significantly elevated in MeHg exposed vs non-exposed mice. Whole body Mn content at day 60 was quantified postmortem by neutron activation analysis, which detected significantly elevated Mn for Treatment B in mice and rats. Overall, we find no evidence to support the use of hair as a valid biomarker for internal exposure to Mn at a neurotoxic level.

Whole body potassium as a biomarker for potassium uptake using a mouse model.

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight [Formula: see text] and [Formula: see text] g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males [Formula: see text] compared to females [Formula: see text]. We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 [Formula: see text] mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

Impact of deformable image registration on dose accumulation applied electrocardiograph-gated 4DCT in the heart and left ventricular myocardium during esophageal cancer radiotherapy.

BACKGROUND: The deformable image registration (DIR) technique has the potential to realize the dose accumulation during radiotherapy. This study will analyze the feasibility of evaluating dose-volume parameters for the heart and left ventricular myocardium (LVM) by applying DIR. METHODS: The electrocardiograph-gated four-dimensional CT (ECG-gated 4DCT) data of 21 patients were analyzed retrospectively. The heart and LVM were contoured on 20 phases of 4DCT (0%, 5%,…,95%). The heart and LVM in the minimum volume/dice similarity coefficient (DSC) phase (Volume min/DSC min) were deformed to the maximum volume/DSC phase (Volume max/ DSC max), which used the intensity-based free-form DIR algorithm of MIM software. The dose was deformed according to the deformation vector. The variations in volume, mean dose (Dmean), V20, V30 and V40 for the heart and LVM before and after DIR were compared, and the reference phase was the Volume max/DSC max phase. RESULTS: For the heart, the difference between the pre- and post-registration Volume min and Volume max were reduced from 13.87 to 1.72%; the DSC was increased from 0.899 to 0.950 between the pre- and post-registration DSC min phase relative to the DSC max phase. The post-registration Dmean, V20, V30 and V40 of the heart were statistically significant compared to those in the Volume max/DSC max phase (p < 0.05). For the LVM, the difference between the pre- and post-registration Volume min and Volume max were only reduced from 18.77 to 17.38%; the DSC reached only 0.733 in the post-registration DSC min phase relative to the DSC max phase. The pre- and post-registration volume, Dmean, V20, V30 and V40 of the LVM were all statistically significant compared to those in the Volume max/DSC max phase (p < 0.05). CONCLUSIONS: There was no significant relationship between the variation in dose-volume parameters and the variation in the volume and morphology for the heart; however, the inconsistency of the variation in the volume and morphology for the LVM was a major factor that led to uncertainty in the dose-volume evaluation. In addition, the individualized local deformation registration technology should be applied in dose accumulation for the heart and LVM.

Definition of the margin of major coronary artery bifurcations during radiotherapy with electrocardiograph-gated 4D-CT.

PURPOSE: The aim was to measure the cardiac motion-induced displacements of major coronary artery bifurcations utilizing electrocardiography (ECG)-gated four-dimensional computed tomography (4D-CT) and to determine the margin of coronary artery bifurcations. METHODS: Thirty-seven female patients who underwent retrospective ECG-gated 4D-CT in inspiratory breath hold (IBH) were enrolled. The left main coronary artery bifurcation (LM), the obtuse marginal branch bifurcation (OM), the first diagonal branch bifurcation (D1), the second diagonal branch bifurcation (D2), the caudal portion of the left anterior descending branch (APX), the first right ventricular artery bifurcation (V) and the acute marginal branch bifurcation (AM) were contoured. The center of the contour of the coronary arterial bifurcations at end systole was defined as the standard, and the margin were then calculated. RESULTS: The margin in the left-right (LR), cranio-caudal (CC), and anterior-posterior (AP) coordinates were as follows: LM 3, 3, and 3 mm; D1 6, 3, and 3 mm; D2 3, 3, and 3 mm; APX 4, 4, and 4 mm; OM 4, 6, and 5 mm; V 6, 8, and 7 mm; and AM 6, 8, and 7 mm, respectively. CONCLUSION: Coronary artery bifurcations should be considered a separate organ at risk (OAR), and different margin should be provided due to the differences resulting from motion displacement. The maximum margin in the LR, CC, and AP coordinates of left coronary artery bifurcations were 6, 6, and 5 mm, and those of the right coronary artery bifurcations were 6, 8, and 7 mm, respectively.

Quantification of variation in dose-volume parameters for the heart, pericardium and left ventricular myocardium during thoracic tumor radiotherapy.

Cardiac activity can induce dose-volume evaluation errors for cardiac structures. The purpose of this study was to quantify the variation in dose-volume parameters for the heart, pericardium and left ventricular myocardium (LVM) throughout the cardiac circle. The heart, pericardium and LVM of 22 patients were contoured on 20 phases of electrocardiography-gated 4D computed tomography (4DCT) images acquired during breath-hold. Radiotherapy plans were designed on 0% phase of the 4DCT images, and the dose distributions of the plans were imported into MIM Maestro and deformed to each phase to generate distributions for all phases. Variations in dose-volume parameters for the heart, pericardium and LVM were compared among different phases. The rates of variation in Dmean for the heart and pericardium were 3.33 ± 1.04% and 2.66 ± 1.15%, respectively. The mean values of the maximum difference in V5, V10, V20, V30 and V40 were all <2% for the heart and pericardium and were not statistically significant (P > 0.05). The rate of variation in Dmean for the LVM reached 87.05 ± 38.34%, and the maximum differences in V5, V10, V20, V30 and V40 were 13.76 ± 4.46%, 13.64 ± 4.33%, 12.84 ± 4.55%, 11.62 ± 4.85% and 3.63 ± 2.56%, respectively; all differences were statistically significant (P < 0.05). Variations in dose-volume parameters were more significant in the LVM than in the heart and pericardium (P < 0.05). The dose-volume parameters for the LVM were significantly influenced by cardiac activity, whereas those for the heart and pericardium were not; therefore, individual dosimetric evaluation and limitation must be performed for the LVM.

Quantification of heart, pericardium, and left ventricular myocardium movements during the cardiac cycle for thoracic tumor radiotherapy.

PURPOSE: The purpose of this study was to quantify variations in the heart, pericardium, and left ventricular myocardium (LVM) caused by cardiac movement using the breath-hold technique. PATIENTS AND METHODS: In this study, the electrocardiography-gated four-dimensional computed tomography (CT) images of 22 patients were analyzed, which were sorted into 20 phases (0-95%) according to the cardiac cycle. The heart, pericardium, and LVM were contoured on each phase of the CT images. The positions, volume, dice similarity coefficient (DSC) in reference to 0% phase, and morphological parameters (max 3D diameter, roundness, spherical disproportion, sphericity, and surface area) in different phases of the heart, pericardium, and LVM were analyzed, which were presented as mean ± standard deviation. RESULTS: The mean values of displacements along the X, Y, and Z axes respectively were as follows: 1.2 mm, 0.6 mm, and 0.6 mm for the heart; 0.5 mm, 0.4 mm, and 0.8 mm for the pericardium; and 1.0 mm, 4.1 mm, and 1.9 mm for the LVM. The maximum variations in volume and DSC respectively were 16.49%±3.85% and 10.08%±2.14% for the heart, 12.62%±3.94% and 5.20%±1.54% for the pericardium, and 24.23%±11.35% and 184.33%±128.61% for the LVM. The differences in the morphological parameters between the maximum and minimum DSC phases for the heart and pericardium were not significantly different (p>0.05) but were significantly different for the LVM (p<0.05). CONCLUSION: The volumetric and morphological variations of the heart were similar to those of pericardium, and all were significantly smaller than those of the LVM. This inconsistency in the volumetric and morphological variations between the LVM and the heart and pericardium indicates that special protection of the LVM should be considered.

The heterogeneous CTV-PTV margins should be given for different parts of tumors during tomotherapy.

OBJECTIVE: The purpose of this study was to evaluate CTV-PTV margins of tumors for tomotherapy. METHODS: Setup errors were analyzed for 151 patients receiving helical tomotherapy treatment. 53 patients had head and neck tumors, 45 had thoracic tumors, 20 had abdominal tumors, and 33 had pelvic tumors. The setup errors were calculated in six directions, i.e. +X (left), -X (right), +Y (head), -Y (foot), +Z (ventral), and -Z (dorsal), after Megavoltage CT (MVCT) images were registered to simulation CT images. And then the CTV-PTV margins were calculated. RESULTS: The setup errors along the +Z direction were significantly higher than that along the -Z direction (p<0.05). The CTV-PTV margins on +X, -X, +Y, -Y, +Z, and -Z directions were asymmetric for all tumors, and the heterogeneity were more remarkable on the +Z and -Z directions. The CTV-PTV margins on +Z and -Z were 4.1 mm, 4.6 mm, 5.2 mm, and 8.4 mm; and 3.9 mm, 7.7 mm, 3.3 mm, and 7.7 mm for head and neck tumors, thoracic tumors, abdominal tumors, and pelvic tumors, respectively. CONCLUSIONS: The CTV-PTV margins for patients with different types of tumors were heterogeneous during tomotherapy. The individual margins of six directions should be given for those patients who accept tomotherapy.