Xerostomia is a common consequence of radiotherapy in head and neck cancer. The objective was to compare the regional radiation dose distribution in patients that developed xerostomia within 6 months ...of radiotherapy and those recovered from xerostomia within 18 months post-radiotherapy. We developed a feature generation pipeline to extract dose volume histogram features from geometrically defined ipsilateral/contralateral parotid glands, submandibular glands, and oral cavity surrogates for each patient. Permutation tests with multiple comparisons were performed to assess the dose difference between injury vs. non-injury and recovery vs. non-recovery. Ridge logistic regression models were applied to predict injury and recovery using clinical features along with dose features (D10-D90) of the subvolumes extracted from oral cavity and salivary gland contours + 3 mm peripheral shell. Model performances were assessed by the area under the receiver operating characteristic curve (AUC) using nested cross-validation. We found that different regional dose/volume metrics patterns exist for injury vs. recovery. Compared to injury, recovery has increased importance to the subvolumes receiving lower dose. Within the subvolumes, injury tends to have increased importance towards D10 from D90. This suggests that different threshold for xerostomia injury and recovery. Injury is induced by the subvolumes receiving higher dose, and the ability to recover can be preserved by further reducing the dose to subvolumes receiving lower dose.
To analyze baseline CT/MR-based image features of salivary glands to predict radiation-induced xerostomia 3-months after head-and-neck cancer (HNC) radiotherapy.
A retrospective analysis was ...performed on 266 HNC patients who were treated using radiotherapy at our institution between 2009 and 2018. CT and T1 post-contrast MR images along with NCI-CTCAE xerostomia grade (3-month follow-up) were prospectively collected at our institution. CT and MR images were registered on which parotid/submandibular glands were contoured. Image features were extracted for ipsilateral/contralateral parotid and submandibular glands relative to the location of the primary tumor. Dose-volume-histogram (DVH) parameters were also acquired. Features were pre-selected based on Spearman correlation before modelling by examining the correlation with xerostomia (p < 0.05). A shrinkage regression analysis of the pre-selected features was performed using LASSO. The internal validity of the variable selection was estimated by repeating the entire variable selection procedure using a leave-one-out-cross-validation. The most frequently selected variables were considered in the final model. A generalized linear regression with repeated ten-fold cross-validation was developed to predict radiation-induced xerostomia at 3-months after radiotherapy. This model was tested in an independent dataset (n = 50) of patients who were treated at the same institution in 2017-2018. We compared the prediction performances under eight conditions (DVH-only, CT-only, MR-only, CT + MR, DVH + CT, DVH + CT + MR, Clinical+CT + MR, and Clinical+DVH + CT + MR) using the area under the receiver operating characteristic curve (ROC-AUC).
Among extracted features, 7 CT, 5 MR, and 2 DVH features were selected. The internal cohort (n = 216) ROC-AUC values for DVH, CT, MR, and Clinical+DVH + CT + MR features were 0.73 ± 0.01, 0.69 ± 0.01, 0.70 ± 0.01, and 0.79 ± 0.01, respectively. The validation cohort (n = 50) ROC-AUC values for DVH, CT, MR, and Clinical+DVH + CT + MR features were 0.63, 0.57, 0.66, and 0.68, respectively. The DVH-ROC was not significantly different than the CT-ROC (p = 0.8) or MR-ROC (p = 0.4). However, the CT + MR-ROC was significantly different than the CT-ROC (p = 0.03), but not the Clinical+DVH + CT + MR model (p = 0.5).
Our results suggest that baseline CT and MR image features may reflect baseline salivary gland function and potential risk for radiation injury. The integration of baseline image features into prediction models has the potential to improve xerostomia risk stratification with the ultimate goal of truly personalized HNC radiotherapy.
Abstract Purpose To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients ...treated with high-dose-rate (HDR) brachytherapy (BT). Methods Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3–6 months post-BT. Diffuse-fibrosis (F Diffuse ) was imaged with a non-contrast dual-echo IR (inversion time TI = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (F Dense ) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting F Diffuse and F Dense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean F Diffuse and F Dense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT F Diffuse and F Dense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT F Dense across IDLs was determined using paired t-tests with Bonferroni correction. Results F Dense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% ( p = .03) in the 100% and 50% IDL, respectively. F Dense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% ( p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in F Dense post-BT ( n = 5, r = .89, p = .04). Post-BT F Diffuse inversely correlated ( n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL. Conclusions Results suggest that F Dense SI 3–6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether F Diffuse and F Dense are accurate biomarkers of fibrotic radiation response.
: To report our design, manufacturing, commissioning and initial clinical experience with a table-mounted range shifter board (RSB) intended to replace the machine-mounted range shifter (MRS) in a ...synchrotron-based pencil beam scanning (PBS) system to reduce penumbra and normal tissue dose for image-guided pediatric craniospinal irradiation (CSI).
: A custom RSB was designed and manufactured from a 3.5 cm thick slab of polymethyl methacrylate (PMMA) to be placed directly under patients, on top of our existing couch top. The relative linear stopping power (RLSP) of the RSB was measured using a multi-layer ionization chamber, and output constancy was measured using an ion chamber. End-to-end tests were performed using the MRS and RSB approaches using an anthropomorphic phantom and radiochromic film measurements. Cone beam CT (CBCT) and 2D planar kV X-ray image quality were compared with and without the RSB present using image quality phantoms. CSI plans were produced using MRS and RSB approaches for two retrospective pediatric patients, and the resultant normal tissue doses were compared.
: The RLSP of the RSB was found to be 1.163 and provided computed penumbra of 6.9 mm in the phantom compared to 11.8 mm using the MRS. Phantom measurements using the RSB demonstrated errors in output constancy, range, and penumbra of 0.3%, -0.8%, and 0.6 mm, respectively. The RSB reduced mean kidney and lung dose compared to the MRS by 57.7% and 46.3%, respectively. The RSB decreased mean CBCT image intensities by 86.8 HU but did not significantly impact CBCT or kV spatial resolution providing acceptable image quality for patient setup.
: A custom RSB for pediatric proton CSI was designed, manufactured, modeled in our TPS, and found to significantly reduce lateral proton beam penumbra compared to a standard MRS while maintaining CBCT and kV image-quality and is in routine use at our center.
Ultrashort echo time MRI biomarkers of asthma Sheikh, Khadija; Guo, Fumin; Capaldi, Dante P.I. ...
Journal of magnetic resonance imaging,
April 2017, Letnik:
45, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Purpose
To develop and assess ultrashort echo‐time (UTE) magnetic resonance imaging (MRI) biomarkers of lung function in asthma patients.
Materials and Methods
Thirty participants including 13 ...healthy volunteers and 17 asthmatics provided written informed consent to UTE and pulmonary function tests in addition to hyperpolarized‐noble‐gas 3T MRI and computed tomography (CT) for asthmatics only. The difference in MRI signal‐intensity (SI) across four lung volumes (full‐expiration, functional‐residual‐capacity FRC, FRC+1L, and full‐inspiration) was determined on a voxel‐by‐voxel basis to generate dynamic proton‐density (DPD) maps. MRI ventilation‐defect‐percent (VDP), UTE SI, and DPD values as well as CT radiodensity were determined for whole lung and individual lobes.
Results
Mean SI at full‐expiration (P < 0.01), FRC (P < 0.05), and DPD (P < 0.01) were greater in healthy volunteers compared to asthmatics. In asthmatics, UTE SI at full‐expiration and DPD were correlated with FEV1/FVC (SI r = 0.73/P = 0.002; DPD r = 0.75/P = 0.003), RV/TLC (SI r = –0.57/P = 0.02), or RV (DPD r = –0.62/P = 0.02), CT radiodensity (SI r = 0.83/P = 0.006; DPD r = 0.71/P = 0.01), and lobar VDP (SI rs = –0.33/P = 0.02; DPD rs = –0.47/P = 0.01).
Conclusion
In patients with asthma, UTE SI and dynamic proton‐density were related to pulmonary function measurements, whole lung and lobar VDP, as well as CT radiodensity. Thus, UTE MRI biomarkers may reflect ventilation heterogeneity and/or gas‐trapping in asthmatics using conventional equipment, making this approach potentially amenable for clinical use.
Level of Evidence: 2
J. Magn. Reson. Imaging 2017;45:1204–1215
This study aimed to quantitatively evaluate the range uncertainties that arise from daily cone-beam CT (CBCT) images for proton dose calculation compared to CT using a measurement-based technique.
...For head and thorax phantoms, wedge-shaped intensity-modulated proton therapy (IMPT) treatment plans were created such that the gradient of the wedge intersected and was measured with a 2D ion chamber array. The measured 2D dose distributions were compared with 2D dose planes extracted from the dose distributions using the IMPT plan calculated on CT and CBCT. Treatment plans of a thymoma cancer patient treated with breath-hold (BH) IMPT were recalculated on 28 CBCTs and 9 CTs, and the resulting dose distributions were compared.
The range uncertainties for the head phantom were determined to be 1.2% with CBCT, compared to 0.5% for CT, whereas the range uncertainties for the thorax phantom were 2.1% with CBCT, compared to 0.8% for CT. The doses calculated on CBCT and CT were similar with similar anatomy changes. For the thymoma patient, the primary source of anatomy change was the BH uncertainty, which could be up to 8 mm in the superior-inferior (SI) direction.
We developed a measurement-based range uncertainty evaluation method with high sensitivity and used it to validate the accuracy of CBCT-based range and dose calculation. Our study demonstrated that the CBCT-based dose calculation could be used for daily dose validation in selected proton patients.
To compare spatially fractionated radiation therapy (GRID) treatment planning techniques using proton pencil-beam-scanning (PBS) and photon therapy.
PBS and volumetric modulated arc therapy (VMAT) ...GRID plans were retrospectively generated for 5 patients with bulky tumors. GRID targets were arranged along the long axis of the gross tumor, spaced 2 and 3 cm apart, and treated with a prescription of 18 Gy. PBS plans used 2- to 3-beam multiple-field optimization with robustness evaluation. Dosimetric parameters including peak-to-edge ratio (PEDR), ratio of dose to 90% of the valley to dose to 10% of the peak VPDR(D90/D10), and volume of normal tissue receiving at least 5 Gy (V5) and 10 Gy (V10) were calculated. The peak-to-valley dose ratio (PVDR), VPDR(D90/D10), and organ-at-risk doses were prospectively assessed in 2 patients undergoing PBS-GRID with pretreatment quality assurance computed tomography (QACT) scans.
PBS and VMAT GRID plans were generated for 5 patients with bulky tumors. Gross tumor volume values ranged from 826 to 1468 cm
. Peak-to-edge ratio for PBS was higher than for VMAT for both spacing scenarios (2-cm spacing,
= .02; 3-cm spacing,
= .01). VPDR(D90/D10) for PBS was higher than for VMAT (2-cm spacing,
= .004; 3-cm spacing,
= .002). Normal tissue V5 was lower for PBS than for VMAT (2-cm spacing,
= .03; 3-cm spacing,
= .02). Normal tissue mean dose was lower with PBS than with VMAT (2-cm spacing,
.03; 3-cm spacing,
.02). Two patients treated using PBS GRID and assessed with pretreatment QACT scans demonstrated robust PVDR, VPDR(D90/D10), and organs-at-risk doses.
The PEDR was significantly higher for PBS than VMAT plans, indicating lower target edge dose. Normal tissue mean dose was significantly lower with PBS than VMAT. PBS GRID may result in lower normal tissue dose compared with VMAT plans, allowing for further dose escalation in patients with bulky disease.
Proton therapy use for breast cancer has grown due to advantages in coverage and potentially reduced late toxicities compared with conventional radiation therapy. We aimed to provide recommendations ...for robustness criteria, daily imaging, and quality assurance computed tomography (QA CT) frequency for these patients.
All patients treated for localized breast cancer at the Johns Hopkins Proton Center between November 2019 and February 2022 were eligible for inclusion. Daily shift information was extracted and examined through control charts. If an adaptive plan was used, the time to replan was recorded. Three and 5 mm setup uncertainty was used to calculate robustness. Robust evaluation of QA CTs was compared with initial robustness range for breast/chest wall and lymph node target coverage.
Sixty-six patients were included: 19 with intact breast, 25 with non-reconstructed chest wall, and 22 with chest wall plus expanders or implants. Sixteen percent, 13%, and 41% of breast, chest wall, and expander/implant patients had a replan. Only patients with expanders or implants required 2 adaptive plans. Daily shift data showed large variation and did not correlate with plan adaptation. Patients without adaptive plans had QA CTs with dose-volume histogram metrics within robustness more frequently than those with adaptive plans. Using 3 mm robustness for patients who did not require an adaptive plan, 91% to 100% of patients had QA CTs within robustness, while 55% to 60% of patients with an adaptive plan had QA CTs within robustness for the axilla, internal mammary nodes, and supraclavicular nodes. Five millimeter setup uncertainty did not significantly improve this.
We recommend using daily cone beam CT because of the large variation in daily setup with 3 mm setup uncertainty in robustness analysis. If daily cone beam CT imaging is not available, then larger setup uncertainty should be used. Two QA CTs should be conducted during treatment if the patient has expanders or implants; otherwise, one QA CT is sufficient.
This is what COPD looks like Sheikh, Khadija; Coxson, Harvey O; Parraga, Grace
Respirology,
February 2016, Letnik:
21, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Despite decades of research, and the growing healthcare and societal burden of chronic obstructive pulmonary disease (COPD), therapeutic COPD breakthroughs have not occurred. Sub‐optimal COPD patient ...phenotyping, an incomplete understanding of COPD pathogenesis and a scarcity of sensitive tools that provide patient‐relevant intermediate endpoints likely all play a role in the lack of new, efficacious COPD interventions. In other words, COPD patients are still diagnosed based on the presence of persistent airflow limitation measured using spirometry. Spirometry measurements reflect the global sum of all the different possible COPD pathologies and perhaps because of this, we lose sight of the different contributions of airway and parenchymal abnormalities. With recent advances in thoracic X‐ray computed tomography (CT) and magnetic resonance imaging (MRI), lung structure and function abnormalities may be regionally identified and measured. These imaging endpoints may serve as biomarkers of COPD that can be used to better phenotype patients. Therefore, here we review novel CT and MRI measurements that help reveal COPD phenotypes and what COPD really ‘looks’ like, beyond spirometric indices. We discuss MR and CT imaging approaches for generating reproducible and sensitive measurements of COPD phenotypes related to pulmonary ventilation and perfusion as well as airway and parenchyma anatomical and morphological features. These measurements may provide a way to advance the development and testing of new COPD interventions and therapies.
The two images illustrate the spatial relationship between 3He MRI ventilation defects and CT of a subject with airways disease dominant COPD. The right image shows co‐registration of 3He MRI static ventilation (blue) and CT (greyscale) with airway rendering (yellow).
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