A Four-dimensional Computed Tomography Generated Internal Target Volume Approach to Paediatric High Risk Neuroblastoma to Reduce Organ at Risk and Normal Tissue Irradiation.

AIMS: The magnitude of upper abdominal organ motion in children may be overestimated by current planning target volumes (PTV). A four-dimensional computed tomography (4DCT) - derived internal target volume (ITV) is frequently used in adult radiotherapy to take respiratory-related organ motion into account. In this study, the dosimetric consequences for target coverage and organs at risk from the use of an ITV approach compared to standard PTV margins in children with high-risk neuroblastoma were investigated. MATERIALS AND METHODS: 14 patients, median age 4.1 years, range 1.5 - 18.9 years, (9 midline targets, 5 lateralised) each had two dual arc volumetric modulated arc therapy (VMAT) plans (14 ×1.5 Gy) generated. One used an ITV-approach; motion information derived from 4DCT (PTV_itv) with a 5mm ITV to PTV expansion, and the other a PTV margin of 10mm from CTV to PTV (PTV_standard). Differences in absolute PTV volume and organ at risk doses are described. RESULTS: The ITV approach resulted in a highly significant reduction in PTV size of 38% (p<0.0001). For midline targets, an ITV approach resulted in a small but statistically significant reduction in combined mean kidney dose of 0.8Gy, p 0.01. Mean heart and lung dose were reduced by an average of 1 Gy with an ITV approach. Non-PTV integral dose from 30.4 Gy L to 27.8 Gy L using an ITV approach. CONCLUSION: An ITV-approach to respiratory related organ motion management in children can significantly reduce absolute PTV volumes, maintain target coverage and reduce dose delivered to normal tissue in proximity to the target. This is an essential step to maximising the benefits of highly conformal radiotherapy techniques including VMAT for this patient group, and in the future with Proton Therapy.

Super-resolution reconstruction of time-resolved four-dimensional computed tomography (TR-4DCT) with multiple breathing cycles based on TR-4DMRI.

BACKGROUND: Respiratory motion irregularities in lung cancer patients are common and can be severe during multi-fractional (∼20 mins/fraction) radiotherapy. However, the current clinical standard of motion management is to use a single-breath respiratory-correlated four-dimension computed tomography (RC-4DCT or 4DCT) to estimate tumor motion to delineate the internal tumor volume (ITV), covering the trajectory of tumor motion, as a treatment target. PURPOSE: To develop a novel multi-breath time-resolved (TR) 4DCT using the super-resolution reconstruction framework with TR 4D magnetic resonance imaging (TR-4DMRI) as guidance for patient-specific breathing irregularity assessment, overcoming the shortcomings of RC-4DCT, including binning artifacts and single-breath limitations. METHODS: Six lung cancer patients participated in the IRB-approved protocol study to receive multiple T1w MRI scans, besides an RC-4DCT scan on the simulation day, including 80 low-resolution (lowR: 5 × 5 × 5 mm3) free-breathing (FB) 3D cine MRFB images in 40 s (2 Hz) and a high-resolution (highR: 2 × 2 × 2 mm3) 3D breath-hold (BH) MRBH image for each patient. A CT (1 × 1 × 3 mm3) image was selected from 10-bin RC-4DCT with minimal binning artifacts and a close diaphragm match (<1 cm) to the MRBH image. A mutual-information-based Freeform deformable image registration (DIR) was used to register the CT and MRBH via the opposite directions (namely F1: C T Source → MR Target BH ${\mathrm{C}}{{{\mathrm{T}}}_{{\mathrm{Source}}}} \to {\mathrm{MR}}_{{\mathrm{Target}}}^{{\mathrm{BH}}}$ and F2: C T Target ← MR Source BH ${\mathrm{C}}{{{\mathrm{T}}}_{{\mathrm{Target}}}} \leftarrow {\mathrm{MR}}_{{\mathrm{Source}}}^{{\mathrm{BH}}}$ ) to establish CT-MR voxel correspondences. An intensity-based enhanced Demons DIR was then applied for MR Source BH → MR Target FB ${\mathrm{MR}}_{{\mathrm{Source}}}^{{\mathrm{BH}}} \to {\mathrm{MR}}_{{\mathrm{Target}}}^{{\mathrm{FB}}}$ , in which the original MRBH was used in D1: C T Source → ( MR Source BH → MR Target FB ) Target ${\mathrm{C}}{{{\mathrm{T}}}_{{\mathrm{Source}}}} \to {{({\mathrm{MR}}_{{\mathrm{Source}}}^{{\mathrm{BH}}} \to {\mathrm{MR}}_{{\mathrm{Target}}}^{{\mathrm{FB}}})}_{{\mathrm{Target}}}}$ , while the deformed MRBH was used in D2: ( C T Target ← MR Source BH ) Source → MR Target FB ${{( \text{C}{{\text{T}}_{\text{Target}}}\leftarrow \text{MR}_{\text{Source}}^{\text{BH}} )}_{\text{Source}}}\to \text{MR}_{\text{Target}}^{\text{FB}}$ . The deformation vector fields (DVFs) obtained from each DIR were composed to apply to the deformed CT (D1) and original CT (D2) to reconstruct TR-4DCT images. A digital 4D-XCAT phantom at the end of inhalation (EOI) and end of exhalation (EOE) with 2.5 cm diaphragmatic motion and three spherical targets (ϕ = 2, 3, 4 cm) were first tested to reconstruct TR-4DCT. For each of the six patients, TR-4DCT images at the EOI, middle (MID), and EOE were reconstructed with both D1 and D2 approaches. TR-4DCT image quality was evaluated with mean distance-to-agreement (MDA) at the diaphragm compared with MRFB, tumor volume ratio (TVR) referenced to MRBH, and tumor shape difference (DICE index) compared with the selected input CT. Additionally, differences in the tumor center of mass (|∆COMD1-D2|), together with TVR and DICE comparison, was assessed in the D1 and D2 reconstructed TR-4DCT images. RESULTS: In the phantom, TR-4DCT quality is assessed by MDA = 2.0 ± 0.8 mm at the diaphragm, TVR = 0.8 ± 0.0 for all tumors, and DICE = 0.83 ± 0.01, 0.85 ± 0.02, 0.88 ± 0.01 for ϕ = 2, 3, 4 cm tumors, respectively. In six patients, the MDA in diaphragm match is -1.6 ± 3.1 mm (D1) and 1.0 ± 3.9 mm (D2) between the reconstructed TR-4DCT and lowR MRFB among 18 images (3 phases/patient). The tumor similarity is TVR = 1.2 ± 0.2 and DICE = 0.70 ± 0.07 for D1 and TVR = 1.4 ± 0.3 (D2) and DICE = 0.73 ± 0.07 for D2. The tumor position difference is |∆COMD1-D2| = 1.2 ± 0.8 mm between D1 and D2 reconstructions. CONCLUSION: The feasibility of super-resolution reconstruction of multi-breathing-cycle TR-4DCT is demonstrated and image quality at the diaphragm and tumor is assessed in both the 4D-XCAT phantom and six lung cancer patients. The similarity of D1 and D2 reconstruction suggests consistent and reliable DIR results. Clinically, TR-4DCT has the potential for breathing irregularity assessment and dosimetry evaluation in radiotherapy.

Optimization of image reconstruction technique for respiratory-gated lung stereotactic body radiotherapy treatment planning using four-dimensional CT: a phantom study.

Patient respiration is characterized by respiratory parameters, such as cycle, amplitude, and baseline drift. In treatment planning using four-dimensional computed tomography (4DCT) images, the target dose may be affected by variations in image reconstruction techniques and respiratory parameters. This study aimed to optimize 4DCT image reconstruction techniques for the treatment planning of lung stereotactic body radiotherapy (SBRT) based on respiratory parameters using respiratory motion phantom. We quantified respiratory parameters using 30 respiratory motion datasets. The 4DCT images were acquired, and the phase- and amplitude-based reconstruction images (RI) were created. The target dose was calculated based on these reconstructed images. Statistical analysis was performed using Pearson's correlation coefficient (r) to determine the relationship between respiratory parameters and target dose in each reconstructed technique and respiratory region. In the inhalation region of phase-based RI, r of the target dose and baseline drift was -0.52. In particular, the target dose was significantly reduced for respiratory parameters with a baseline drift of 0.8 mm/s and above. No other respiratory parameters or respiratory regions were significantly correlated with target dose in phase-based RI. In amplitude-based RI, there were no significant differences in the correlation between all respiratory parameters and target dose in the exhalation or inhalation regions. These results showed that the target dose of the amplitude-based RI did not depend on changes in respiratory parameters or respiratory regions, compared to the phase-based RI. However, it is possible to guarantee the target dose by considering respiratory parameters during the inhalation region of the phase-based RI.

Refining the role of presurgical PET/4D-CT in a large series of patients with primary hyperparathyroidism undergoing [18F]Fluorocholine PET/CT.

BACKGROUND: 4D-CT has garnered attention as complementary imaging for patients with primary hyperparathyroidism (pHPT). Herein we evaluated a diagnostic strategy using [18F]Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT), followed by 4D-CT integrated into PET/4D-CT after negative/inconclusive PET/CT results in a single-center retrospective cohort of 166 pHPT patients who underwent parathyroidectomy after [18F]Fluorocholine PET/4D-CT. METHODS: PET/CT and 4D-CT images were interpreted by three nuclear medicine physicians and one expert radiologist. Pathological findings were documented, and concordance rates were assessed. PET/CT results were categorized as positive/negative, with positive cases rated on a 3-level certitude scale: low, moderate, high. Inconclusive cases included low/moderate positivity. The added value of PET/4D-CT was assessed for negative/inconclusive cases through joint reading. RESULTS: PET/CT lesion-based analysis showed almost perfect interobserver concordance (Cohen's kappa >.8). Across the cohort, PET/CT had a sensitivity of 83%, specificity of 97%, PPV of 90% and NPV of 94%. For 4D-CT, these values were sensitivity: 53%, specificity: 84%, PPV: 56% and NPV: 82%. PET/CT was significantly more accurate than 4D-CT. Among 44 patients with negative/inconclusive results, PET/CT had sensitivity: 60%, specificity: 91%, PPV: 71% and NPV: 86%. In the same patients, sensitivity and specificity of the sequential diagnostic algorithm increased to 80% and 97%, showing significantly better global accuracy (92% vs. 83%) than standard PET/CT. CONCLUSIONS: We support a personalized imaging algorithm for pHPT, placing [18F]Fluorocholine PET/CT at the forefront, followed by 4D-CT integrated into PET/4D-CT in the same imaging session for negative/inconclusive results. When PET/CT results are clearly positive, the additional sensitivity benefit of 4D-CT is minimal.

[A Comparison of Tumor Respiratory Motion Evaluation Methods Using Dynamic Thorax Motion Phantom].

PURPOSE: We evaluated the measurement accuracy and time efficiency of the tumor respiratory motion evaluation methods using a dynamic thorax motion phantom. METHODS: A total of 12 patterns of 4DCT images with different tumor displacements and artifacts were used for the measurement. Three methods were employed to measure tumor motion. The first method was the manual delineation of the tumor on each phase CT image with a treatment planning system (RTPS [Manual]). The second method was the automatic delineation of the tumor structure by deformation and copying (RTPS [Auto]). The third method was tumor motion analysis software (Simple 4D Analysis Ver.1.3.1 [Simple 4D]; Triangle Products, Chiba, Japan). For each method, the difference between the phantom motion and the measured value was determined. RESULTS: The differences (mean±standard deviation: SD) in the superior-inferior direction for RTPS (Manual), RTPS (Auto), and Simple 4D in the without-artifact images were -0.6 mm±0.6 mm, -5.0 mm±2.2 mm, and -1.0 mm±0.0 mm, respectively. The difference in the left-right and anterior-posterior directions was within 1 mm for all methods. Furthermore, the time required for Simple 4D was shorter than for the other methods. CONCLUSION: Simple 4D showed the comparable measurement accuracy and improvement time efficiency to RTPS (Manual) and RTPS (Auto), and was useful for tumor respiratory motion analysis.

The polar vessel sign: insights from CT imaging analysis in Asian Indian primary hyperparathyroidism.

PURPOSE: Data on the polar vessel sign (enlarged feeding vessel terminating in parathyroid lesions) on four-dimensional computed tomography (4D-CT) is limited. We performed a retrospective analysis to determine the prevalence, predictors, and adjunctive utility of polar vessel sign in pre-operative 4D-CT of patients with primary hyperparathyroidism (PHPT). METHODS: One radiologist blinded to the patients' details reported the 4D-CT of eighty-four operated patients with histopathology-proven single-gland PHPT. Two protocols were used to obtain arterial-phase images: timed via bolus tracking (n = 41) or fixed at 20 s after contrast injection (n = 43). RESULTS: Seventy-one patients were symptomatic for PHPT, with median serum calcium 12.1 mg/dL. On the arterial phase of 4D-CT, 88.1% of lesions had the polar vessel sign, including 7/9 asymptomatic patients, 6/6 parathyroid carcinomas, and 3/4 ectopic(1:mediastinum, 2:thyro-thymic ligament). Predictors of polar vessel sign were maximum lesion dimension (2.2 vs. 1.4 cm; P = 0.03), solid-cystic CT morphology (47.3% vs. none; P = 0.004), and bolus tracking-timed arterial phase (55.4% vs. none; P = 0.001). Of these, bolus tracking improved the polar vessel's visualization (100% vs. 76.7%; P = 0.001) independent of lesion dimension and solid-cystic morphology. The latter two predicted polar vessel sign in images obtained at a fixed interval (20 s). A significantly lower proportion of bolus tracking-timed scans had lesion percentage arterial enhancement (PAE) < 128.9% (2/41 vs. 9/43; P = 0.04). Even with suboptimal PAE, the polar vessel helped identify 9/11 lesions. CONCLUSION: The polar vessel sign demonstrated an additive role to PAE during CT reporting. Bolus tracking is valuable in optimizing vessel and tumor arterial enhancement and is easily incorporated into parathyroid 4D-CT protocol.

Regional ventilation dynamics of electrical impedance tomography validated with four-dimensional computed tomography: single-center, prospective, observational study.

BACKGROUND: The dynamic regional accuracy of electrical impedance tomography has not yet been validated. We aimed to compare the regional accuracy of electrical impedance tomography with that of four-dimensional computed tomography during dynamic ventilation. METHODS: This single-center, prospective, observational study conducted in a general intensive care unit included adult patients receiving mechanical ventilation from July 2021 to February 2024. The patients were mechanically ventilated passively and underwent electrical impedance tomography and four-dimensional computed tomography on the same day. RESULTS: Overall, 45 patients were analyzed. The correlation coefficients in regional dynamic ventilation between four-dimensional computed tomography and electrical impedance tomography in each region were 0.963, 0.963, 0.835 (ventral, central, and dorsal, respectively) in the right lung and 0.947, 0.927, 0.823 (ventral, central, and dorsal, respectively) in the left lung. The correlation coefficient was low when the regional ventilation distribution detected by the electrical impedance tomography was < 2%. After excluding nine patients with a regional ventilation distribution of < 2%, the ventral, central, and dorsal correlation coefficients were 0.963, 0.963, and 0.946 in the right lung and 0.942, 0.924, and 0.951, respectively, in the left lung. CONCLUSIONS: Regional ventilation using electrical impedance tomography during dynamic ventilation was highly accurate and consistent with the time phase compared to four-dimensional computed tomography. Given the high correlation between these modalities, they can contribute significantly to further studies on regional ventilation dynamics. Trial registration number ClinicalTrials.gov (No. UMIN00044386).

Four-dimensional computed tomography and ultrasonography for prediction of pathological parathyroid location: a retrospective review of a single surgeon's patients at a single institution.

Background: Pre-operative imaging is a well-established practice for managing hyperparathyroidism with the plan for excision; however, there is a paucity of information regarding the success rate of concordant imaging studies. Our goal was to compare the accuracy (sensitivity) of four-dimensional computed tomography (4DCT) and ultrasound (US) when predicting the side and quadrant of parathyroid lesions, confirmed with surgical location (from a single surgeon). Methods: A retrospective review of 437 patients from a single surgeon undergoing parathyroidectomy from December 2013 to January 2020 at an academic medical center was performed. Masses >5 mm in dimension in eutopic parathyroid locations were identified as possible parathyroid lesions on 4DCT. A unique codified system was utilized to accurately record imaging results for each modality and compared to surgical findings. Results: Four hundred and thirty-seven patients underwent parathyroid surgery, of those 431 underwent 4DCT, 413 underwent US, and 408 underwent both. 4DCT accurately lateralized lesions in 319 (74.0%; N=431). US lateralized lesions in 265 (64.2%; N=413). The sensitivity for lateralization was 81.2% and 69.9% for 4DCT and US, respectively. Conclusions: 4DCT and US identify the majority of parathyroid lesions. 4DCT outperformed US in lateralization yet both modalities remain useful and are complimentary in planning for successful parathyroidectomy. Newer imaging approaches such as 18F-choline positron emission tomography/computed tomography (PET/CT) and artificial intelligence as an augmentation to imaging review may play in role to identify parathyroid adenomas/hyperplasia, but their roles have yet to be clearly defined.

Is clinical target volume necessary for locally advanced non-small cell lung cancer treated with 4D-CT intensity-modulated radiation therapy.

BACKGROUND: A dosimetric evaluation is still lacking in terms of clinical target volume (CTV) omission in stage III patients treated with 4D-CT Intensity-Modulated Radiation Therapy (IMRT). METHODS: 49 stage III NSCLC patients received 4D-CT IMRT were reviewed. Target volumes and organs at risk (OARs) were re-delineated. Four IMRT plans were conducted retrospectively to deliver different prescribed dose (74 Gy-60 Gy), and with or without CTV implementation. Dose and volume histogram (DVH) parameters were collected and compared. RESULTS: In the PTV-g 60 Gy plan (PTV-g refers to the PTV generated from the internal gross tumor volume), only 5 of 49 patients had the isodose ≥ 50 Gy line covering at least 95% of the PTV-c (PTV-c refers to the PTV generated from the internal CTV) volume. When the prescribed dose was elevated to 74 Gy to the PTV-g, 33 of 49 patients could have the isodose ≥ 50 Gy line covering at least 95% of the PTV-c volume. In terms of OARs protection, the SIB-IMRT plan showed the lowest value of V5, V20, and mean dose of lung, had the lowest V55 of esophagus, and the lowest estimated radiation doses to immune cells (EDIC). The V20, V30, and mean dose of heart was lower in the simultaneous integrated boost (SIB) IMRT (SIB-IMRT) plan than that of the PTV-c 60 Gy plan. CONCLUSIONS: CTV omission was not suitable for stage III patients when the prescribed dose to PTV-g was 60 Gy in the era of 4D-CT IMRT. CTV omission plus high dose to PTV-g (74 Gy for example) warranted further exploration. The SIB-IMRT plan had the best protection to normal tissue including lymphocytes, and might be the optimal choice.

Advances in CT-based lung function imaging for thoracic radiotherapy.

The objective of this review is to examine the potential benefits and challenges of CT-based lung function imaging in radiotherapy over recent decades. This includes reviewing background information, defining related concepts, classifying and reviewing existing studies, and proposing directions for further investigation. The lung function imaging techniques reviewed herein encompass CT-based methods, specifically utilizing phase-resolved four-dimensional CT (4D-CT) or end-inspiratory and end-expiratory CT scans, to delineate distinct functional regions within the lungs. These methods extract crucial functional parameters, including lung volume and ventilation distribution, pivotal for assessing and characterizing the functional capacity of the lungs. CT-based lung ventilation imaging offers numerous advantages, notably in the realm of thoracic radiotherapy. By utilizing routine CT scans, additional radiation exposure and financial burdens on patients can be avoided. This imaging technique also enables the identification of different functional areas of the lung, which is crucial for minimizing radiation exposure to healthy lung tissue and predicting and detecting lung injury during treatment. In conclusion, CT-based lung function imaging holds significant promise for improving the effectiveness and safety of thoracic radiotherapy. Nevertheless, challenges persist, necessitating further research to address limitations and optimize clinical utilization. Overall, this review highlights the importance of CT-based lung function imaging as a valuable tool in radiotherapy planning and lung injury monitoring.

A novel internal target volume definition based on velocity and time of respiratory target motion for external beam radiotherapy.

This study aimed to develop a novel internal target volume (ITV) definition for respiratory motion targets, considering target motion velocity and time. The proposed ITV was evaluated in respiratory-gated radiotherapy. An ITV modified with target motion velocity and time (ITVvt) was defined as an ITV that includes a target motion based on target motion velocity and time. The target motion velocity was calculated using four-dimensional computed tomography (4DCT) images. The ITVvts were created from phantom and clinical 4DCT images. The phantom 4DCT images were acquired using a solid phantom that moved with a sinusoidal waveform (peak-to-peak amplitudes of 10 and 20 mm and cycles of 2-6 s). The clinical 4DCT images were obtained from eight lung cancer cases. In respiratory-gated radiotherapy, the ITVvt was compared with conventional ITVs for beam times of 0.5-2 s within the gating window. The conventional ITV was created by adding a uniform margin as the maximum motion within the gating window. In the phantom images, the maximum volume difference between the ITVvt and conventional ITV was -81.9%. In the clinical images, the maximum volume difference was -53.6%. Shorter respiratory cycles and longer BTs resulted in smaller ITVvt compared with the conventional ITV. Therefore, the proposed ITVvt plan could be used to reduce treatment volumes and doses to normal tissues.

Impact of breathing signal-guided dose modulation on step-and-shoot 4D CT image reconstruction.

BACKGROUND: Breathing signal-guided 4D CT sequence scanning such as the intelligent 4D CT (i4DCT) approach reduces imaging artifacts compared to conventional 4D CT. By design, i4DCT captures entire breathing cycles during beam-on periods, leading to redundant projection data and increased radiation exposure to patients exhibiting prolonged exhalation phases. A recently proposed breathing-guided dose modulation (DM) algorithm promises to lower the imaging dose by temporarily reducing the CT tube current, but the impact on image reconstruction and the resulting images have not been investigated. PURPOSE: We evaluate the impact of breathing signal-guided DM on 4D CT image reconstruction and corresponding images. METHODS: This study is designed as a comparative and retrospective analysis based on 104 4D CT datasets. Each dataset underwent retrospective reconstruction twice: (a) utilizing the acquired clinical projection data for reconstruction, which yields reference image data, and (b) excluding projections acquired during potential DM phases from image reconstruction, resulting in DM-affected image data. Resulting images underwent automatic organ segmentation (lung/liver). (Dis)Similarity of reference and DM-affected images were quantified by the Dice coefficient of the entire organ masks and the organ overlaps within the DM-affected slices. Further, for lung cases, (a) and (b) were deformably registered and median magnitudes of the obtained displacement field were computed. Eventually, for 17 lung cases, gross tumor volumes (GTV) were recontoured on both (a) and (b). Target volume similarity was quantified by the Hausdorff distance. RESULTS: DM resulted in a median imaging dose reduction of 15.4% (interquartile range [IQR]: 11.3%-19.9%) for the present patient cohort. Dice coefficients for lung ( n = 73 $n=73$ ) and liver ( n = 31 $n=31$ ) patients were consistently high for both the entire organs and the DM-affected slices (IQR lung: 0.985 / 0.982 $0.985/0.982$ [entire lung/DM-affected slices only] to 0.992 / 0.989 $0.992/0.989$ ; IQR liver: 0.977 / 0.972 $0.977/0.972$ to 0.986 / 0.986 $0.986/0.986$ ), demonstrating that DM did not cause organ distortions or alterations. Median displacements for DM-affected to reference image registration varied; however, only two out of 73 cases exhibited a median displacement larger than one isotropic 1 mm 3 ${\rm mm}^3$ voxel size. The impact on GTV definition for the end-exhalation phase was also minor (median Hausdorff distance: 0.38 mm, IQR: 0.15-0.46 mm). CONCLUSION: This study demonstrates that breathing signal-guided DM has a minimal impact on image reconstruction and image appearance while improving patient safety by reducing dose exposure.

Optimizing Choice of Skin Surrogates for Surface-Guided Stereotactic Body Radiotherapy of Lung Lesions Using Four-Dimensional Computed Tomography.

Image-guided radiotherapy supported by surface guidance can help to track lower lung lesions' respiratory motion while reducing a patient's exposure to ionizing radiation. However, it is not always clear how the skin's respiratory motion magnitude and its correlation with the lung lesion's respiratory motion vary between different skin regions of interest (ROI). Four-dimensional computed tomography (4DCT) images provide information on both the skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. An analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on the respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing a lower lung lobe lesion, as well as the respiratory motion correlations between the nine ROIs and the TS. The effects of gender and the adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between the ROIs in both the respiratory motion magnitudes and their correlations with the TS have been detected. An overall negative correlation between the ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between the adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. The respiratory magnitudes in regions without rib support tend to be larger for men than for women, but no differences in the ROI-to-TS correlation between sexes have been detected. The described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

Imaging Recommendations for Diagnosis and Management of Primary Parathyroid Pathologies: A Comprehensive Review.

Parathyroid pathologies are suspected based on the biochemical alterations and clinical manifestations, and the predominant roles of imaging in primary hyperparathyroidism are localisation of tumour within parathyroid glands, surgical planning, and to look for any ectopic parathyroid tissue in the setting of recurrent disease. This article provides a comprehensive review of embryology and anatomical variations of parathyroid glands and their clinical relevance, surgical anatomy of parathyroid glands, differentiation between multiglandular parathyroid disease, solitary adenoma, atypical parathyroid tumour, and parathyroid carcinoma. The roles, advantages and limitations of ultrasound, four-dimensional computed tomography (4DCT), radiolabelled technetium-99 (99mTc) sestamibi or dual tracer 99mTc pertechnetate and 99mTc-sestamibi with or without single photon emission computed tomography (SPECT) or SPECT/CT, dynamic enhanced magnetic resonance imaging (4DMRI), and fluoro-choline positron emission tomography (18F-FCH PET) or [11C] Methionine (11C -MET) PET in the management of parathyroid lesions have been extensively discussed in this article. The role of fluorodeoxyglucose PET (FDG-PET) has also been elucidated in this article. Management guidelines for parathyroid carcinoma proposed by the American Society of Clinical Oncology (ASCO) have also been described. An algorithm for management of parathyroid lesions has been provided at the end to serve as a quick reference guide for radiologists, clinicians and surgeons.

Stability analysis of patient-specific 4DCT- and 4DCBCT-based correspondence models.

BACKGROUND: Surrogate-based motion compensation in stereotactic body radiation therapy (SBRT) strongly relies on a constant relationship between an external breathing signal and the internal tumor motion over the course of treatment, that is, a stable patient-specific correspondence model. PURPOSE: This study aims to develop methods for analyzing the stability of correspondence models by integrating planning 4DCT and pretreatment 4D cone-beam computed tomography (4DCBCT) data and assessing the relation to patient-specific clinical parameters. METHODS: For correspondence modeling, a regression-based approach is applied, correlating patient-specific internal motion (vector fields computed by deformable image registration) and external breathing signals (recorded by Varian's RPM and RGSC system). To analyze correspondence model stability, two complementary methods are proposed. (1) Target volume-based analysis: 4DCBCT-based correspondence models predict clinical target volumes (GTV and internal target volume [ITV]) within the planning 4DCT, which are evaluated by overlap and distance measures (Dice similarity coefficient [DSC]/average symmetric surface distance [ASSD]). (2) System matrix-based analysis: 4DCBCT-based regression models are compared to 4DCT-based models using mean squared difference (MSD) and principal component analysis of the system matrices. Stability analysis results are correlated with clinical parameters. Both methods are applied to a dataset of 214 pretreatment 4DCBCT scans (Varian TrueBeam) from a cohort of 46 lung tumor patients treated with ITV-based SBRT (planning 4DCTs acquired with Siemens AS Open and SOMATOM go.OPEN Pro CT scanners). RESULTS: Consistent results across the two complementary analysis approaches (Spearman correlation coefficient of 0.6 / 0.7 $0.6/ 0.7$ between system matrix-based MSD and GTV-based DSC/ASSD) were observed. Analysis showed that stability was not predominant, with 114/214 fraction-wise models not surpassing a threshold of D S C > 0.7 $DSC > 0.7$ for the GTV, and only 14/46 patients demonstrating a D S C > 0.7 $DSC > 0.7$ in all fractions. Model stability did not degrade over the course of treatment. The mean GTV-based DSC is 0.59 ± 0.26 $0.59\pm 0.26$ (mean ASSD of 2.83 ± 3.37 $2.83\pm 3.37$ ) and the respective ITV-based DSC is 0.69 ± 0.20 $0.69\pm 0.20$ (mean ASSD of 2.35 ± 1.81 $2.35\pm 1.81$ ). The clinical parameters showed a strong correlation between smaller tumor motion ranges and increased stability. CONCLUSIONS: The proposed methods identify patients with unstable correspondence models prior to each treatment fraction, serving as direct indicators for the necessity of replanning and adaptive treatment approaches to account for internal-external motion variations throughout the course of treatment.

Improving the Feasibility of Mitigating Phase Errors in 4DCT caused by a Random Reference Breathing Pattern in the Quasar Phantom and the Role of Slice Thickness.

PURPOSE: The study aimed to validate a method for minimizing phase errors by combining full-length lung 4DCT (f4DCT) scans with shorter tumor-restricted 4DCT (s4DCT) scans. It assessed the feasibility of integrating two scans one covering the entire phantom length and the other focused on the tumor area. The study also evaluated the impact of Maximum Intensity Projection (MIP) volume and imaging dose for different slice thicknesses (2.5mm and 1.25mm) in both full-length and short target-restricted 4DCT scans. METHODS: The study utilized the Quasar Programmable Respiratory Motion Phantom, simulating tumor motion with a variable lung insert. The setup included a tumor replica and a six-dot IR reflector marker on the breathing platform. The objective was to analyze volume differences in fMIP_2.5mm compared to sMIP_1.25mm within their respective 4D_MIP CT series. This involved varying breathing periods (2.5s, 3.0s, 4.0s, and 5.0s) and longitudinal tumor sizes (6mm, 8mm, and 10mm). The study also assessed exposure time and expected CTDIvol of s4D_2.5mm and s4D_1.25mm for different breathing periods (5.0s to 2.0s) in the sinusoidal wave motion of the six-dot marker on the breathing platform. RESULTS: Conducting two consecutive 4DCT scans is viable for patients with challenging breathing patterns or when the initial lung tumor scan is in close proximity to the tumor location, eliminating the need for an additional full-length 4DCT. The analysis involves assessing MIP volume, imaging dose (CTDIvol), and exposure time. Longitudinal tumor shifts for 6mm are [16.6-17.2] in fMIP_2.5mm and [16.8-17.5] in sMIP_1.25mm, for 8mm [17.2-18.3] in fMIP_2.5mm and [17.8-18.4] in sMIP_1.25mm, and for 10mm [19-19.9] in fMIP_2.5mm and [19.4-20] in sMIP_1.25mm (p≥ 0.005), respectively. CONCLUSION: The Quasar Programmable Respiratory Motion Phantom accurately replicated varied breathing patterns and tumor motions. Comprehensive analysis was facilitated through detailed manual segmentation of Internal Target Volumes and Internal Gross Target Volumes.

Establishing a 4D-CT lung function related volumetric dose model to reduce radiation pneumonia.

In order to study how to use pulmonary functional imaging obtained through 4D-CT fusion for radiotherapy planning, and transform traditional dose volume parameters into functional dose volume parameters, a functional dose volume parameter model that may reduce level 2 and above radiation pneumonia was obtained. 41 pulmonary tumor patients who underwent 4D-CT in our department from 2020 to 2023 were included. MIM Software (MIM 7.0.7; MIM Software Inc., Cleveland, OH, USA) was used to register adjacent phase CT images in the 4D-CT series. The three-dimensional displacement vector of CT pixels was obtained when changing from one respiratory state to another respiratory state, and this three-dimensional vector was quantitatively analyzed. Thus, a color schematic diagram reflecting the degree of changes in lung CT pixels during the breathing process, namely the distribution of ventilation function strength, is obtained. Finally, this diagram is fused with the localization CT image. Select areas with Jacobi > 1.2 as high lung function areas and outline them as fLung. Import the patient's DVH image again, fuse the lung ventilation image with the localization CT image, and obtain the volume of fLung different doses (V60, V55, V50, V45, V40, V35, V30, V25, V20, V15, V10, V5). Analyze the functional dose volume parameters related to the risk of level 2 and above radiation pneumonia using R language and create a predictive model. By using stepwise regression and optimal subset method to screen for independent variables V35, V30, V25, V20, V15, and V10, the prediction formula was obtained as follows: Risk = 0.23656-0.13784 * V35 + 0.37445 * V30-0.38317 * V25 + 0.21341 * V20-0.10209 * V15 + 0.03815 * V10. These six independent variables were analyzed using a column chart, and a calibration curve was drawn using the calibrate function. It was found that the Bias corrected line and the Apparent line were very close to the Ideal line, The consistency between the predicted value and the actual value is very good. By using the ROC function to plot the ROC curve and calculating the area under the curve: 0.8475, 95% CI 0.7237-0.9713, it can also be determined that the accuracy of the model is very high. In addition, we also used Lasso method and random forest method to filter out independent variables with different results, but the calibration curve drawn by the calibration function confirmed poor prediction performance. The function dose volume parameters V35, V30, V25, V20, V15, and V10 obtained through 4D-CT are key factors affecting radiation pneumonia. Establishing a predictive model can provide more accurate lung restriction basis for clinical radiotherapy planning.

A back propagation neural network based respiratory motion modelling method.

BACKGROUND: This study presents the development of a backpropagation neural network-based respiratory motion modelling method (BP-RMM) for precisely tracking arbitrary points within lung tissue throughout free respiration, encompassing deep inspiration and expiration phases. METHODS: Internal and external respiratory data from four-dimensional computed tomography (4DCT) are processed using various artificial intelligence algorithms. Data augmentation through polynomial interpolation is employed to enhance dataset robustness. A BP neural network is then constructed to comprehensively track lung tissue movement. RESULTS: The BP-RMM demonstrates promising accuracy. In cases from the public 4DCT dataset, the average target registration error (TRE) between authentic deep respiration phases and those forecasted by BP-RMM for 75 marked points is 1.819 mm. Notably, TRE for normal respiration phases is significantly lower, with a minimum error of 0.511 mm. CONCLUSIONS: The proposed method is validated for its high accuracy and robustness, establishing it as a promising tool for surgical navigation within the lung.

Optimized raw data selection for artifact reduction of breathing controlled four-dimensional sequence scanning.

Background and purpose: Even with most breathing-controlled four-dimensional computed tomography (4DCT) algorithms image artifacts caused by single significant longer breathing still occur, resulting in negative consequences for radiotherapy. Our study presents first phantom examinations of a new optimized raw data selection and binning algorithm, aiming to improve image quality and geometric accuracy without additional dose exposure. Materials and methods: To validate the new approach, phantom measurements were performed to assess geometric accuracy (volume fidelity, root mean square error, Dice coefficient of volume overlap) for one- and three-dimensional tumor motion trajectories with and without considering motion hysteresis effects. Scans without significantly longer breathing cycles served as references. Results: Median volume deviations between optimized approach and reference of at maximum 1% were obtained considering all movements. In comparison, standard reconstruction yielded median deviations of 9%, 21% and 12% for one-dimensional, three-dimensional, and hysteresis motion, respectively. Measurements in one- and three-dimensional directions reached a median Dice coefficient of 0.970 ± 0.013 and 0.975 ± 0.012, respectively, but only 0.918 ± 0.075 for hysteresis motions averaged over all measurements for the optimized selection. However, for the standard reconstruction median Dice coefficients were 0.845 ± 0.200, 0.868 ± 0.205 and 0.915 ± 0.075 for one- and three-dimensional as well as hysteresis motions, respectively. Median root mean square errors for the optimized algorithm were 30 ± 16 HU2 and 120 ± 90 HU2 for three-dimensional and hysteresis motions, compared to 212 ± 145 HU2 and 130 ± 131 HU2 for the standard reconstruction. Conclusions: The algorithm was proven to reduce 4DCT-related artifacts due to missing projection data without further dose exposure. An improvement in radiotherapy treatment planning due to better image quality can be expected.

Data-driven gating (DDG)-based motion match for improved CTAC registration.

BACKGROUND: Respiratory motion artefacts are a pitfall in thoracic PET/CT imaging. A source of these motion artefacts within PET images is the CT used for attenuation correction of the images. The arbitrary respiratory phase in which the helical CT ( CT helical ) is acquired often causes misregistration between PET and CT images, leading to inaccurate attenuation correction of the PET image. As a result, errors in tumour delineation or lesion uptake values can occur. To minimise the effect of motion in PET/CT imaging, a data-driven gating (DDG)-based motion match (MM) algorithm has been developed that estimates the phase of the CT helical , and subsequently warps this CT to a given phase of the respiratory cycle, allowing it to be phase-matched to the PET. A set of data was used which had four-dimensional CT (4DCT) acquired alongside PET/CT. The 4DCT allowed ground truth CT phases to be generated and compared to the algorithm-generated motion match CT (MMCT). Measurements of liver and lesion margin positions were taken across CT images to determine any differences and establish how well the algorithm performed concerning warping the CT helical to a given phase (end-of-expiration, EE). RESULTS: Whilst there was a minor significance in the liver measurement between the 4DCT and MMCT ( p = 0.045 ), no significant differences were found between the 4DCT or MMCT for lesion measurements ( p = 1.0 ). In all instances, the CT helical was found to be significantly different from the 4DCT ( p < 0.001 ). Consequently, the 4DCT and MMCT can be considered equivalent with respect to warped CT generation, showing the DDG-based MM algorithm to be successful. CONCLUSION: The MM algorithm successfully enables the phase-matching of a CT helical to the EE of a ground truth 4DCT. This would reduce the motion artefacts caused by PET/CT registration without requiring additional patient dose (required for a 4DCT).