Purpose

In radiation treatment planning for thoracic and abdominal tumors, 4D-MRI has shown promise in respiratory motion characterization with improved soft-tissue contrast compared to clinical standard, 4D computed tomography (4D-CT). This study aimed to further improve vessel-tissue contrast and overall image quality in 3D radial sampling-based 4D-MRI using a slab-selective (SS) excitation approach.

Methods

The technique was implemented in a 3D radial sampling with self-gating-based k-space sorting sequence. The SS excitation approach was compared to a non-selective (NS) approach in six cancer patients and two healthy volunteers at 3T. Improvements in vessel-tissue contrast ratio (CR) and vessel signal-to-noise ratio (SNR) were analyzed in five of the eight subjects. Image quality was visually assessed in all subjects on a 4-point scale (0: poor; 3: excellent). Tumor (patients) and pancreas (healthy) motion trajectories were compared between the two imaging approaches.

Results

Compared with NS-4D-MRI, SS-4D-MRI significantly improved the overall vessel-tissue CR (2.60 ± 3.97 vs. 1.03 ± 1.44, P < 0.05), SNR (63.33 ± 38.45 vs. 35.74 ± 28.59, P < 0.05), and image quality score (2.6 ± 0.5 vs. 1.4 ± 0.5, P = 0.02). Motion trajectories from the two approaches exhibited strong correlation in the superior-inferior (0.96 ± 0.06), but weaker in the anterior-posterior (0.78 ± 0.24) and medial-lateral directions (0.46 ± 0.44).

Conclusions

The proposed 4D-MRI with slab-selectively excited 3D radial sampling allows for improved blood SNR, vessel-tissue CR, and image quality.

Based on 4D-CT, we aimed to characterize the pattern of morphological changes in lung tumors during respiration, and investigated its potential in non-invasively differentiating lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). We applied a 3D surface analysis on 22 tumors (13 AC, 9 SCC) to investigate the tumor regional morphological fluctuations in response to respiration phases. Tumor surface vertices among ten respiratory phases were matched using surface-based registration, and the shape descriptors (ρ and detJ) were calculated and tracked across respiration stages in a regionally aligned scenario. Pair-wise group comparisons were performed between lung AC and SCC subtypes, in terms of ratios of maximal shape changes as well as correlation coefficients between tumor shape and respiratory stage indicators from the lung. AC type tumors had averaged larger surface measurements at exhale than at inhale, and these surface measurements were negatively correlated with lung volumes across respiratory stages. In contrast, SCC type tumors had averaged smaller surface measurements at exhale than at inhale, and the correlations with lung volumes were positive. The group differences in maximal shape changes as well as correlations were both statistically significant (p  <  0.05). We developed a non-invasive lung tumor sub-type detection pipeline based on respiration-induced tumor surface deformation. Significant differences in deformation patterns were detected between lung AC and SCC. The derived surface measurements may potentially serve as a new non-invasive imaging biomarker of lung cancer subtypes.

Purpose

To introduce a novel surface-based dose mapping method to improve quantitative bladder dosimetric assessment in prostate cancer (PC) radiotherapy.

Methods

Based on the planning and daily pre and postfraction MRIs of 12 PC patients, bladder surface models (SMs) were generated on manually delineated contours and regionally aligned via surface-based registration. Subsequently, bladder surface dose models (SDMs) were created using face-wise dose sampling. To determine the bladder intrafractional and interfractional motion and dose variation, we performed a pose analysis between pre and postfraction bladder SMs, as well as surface mapping for fractional SMs. Discrepancies between the received dose, accumulated from daily SDMs, and the planned dose were then assessed on the corresponding SDMs. Complementary to the surface dose mapping, dose surface histogram (DSH)-based comparisons were also performed.

Results

The intrafraction pose analysis revealed a significant (p < 0.05) bladder expansion, as well as an anterior/superior drift during the treatment. The intrafraction motion substantially altered dose to mid-bladder body, but not the bladder surface areas distal to or contiguous with the target. A similar pattern of dose variations was also detected by interfraction comparisons. With surface registration to the common SM, the cumulative bladder dose significantly differs from the planned dose. The discrepancy is evident in the mid-posterior range that corresponds to a mid- to high-dose region. The received DSH significantly differs from the planned DSH after permutation correction (p = 0.0122), while the overall surface-based comparison after multiple comparison correction is nonsignificant (p = 0.0800).

Conclusions

We developed a novel surface-based intra and interdose mapping framework applied to a unique daily MR dataset for image-guided radiotherapy. The framework identified significant intrafraction bladder positional changes, localized the intra and interfraction variations, and quantified planned versus received dose differences on the bladder surface. The result indicates the importance of adopting the motion-integrated bladder SDM for bladder dose management.

Background and purpose

Adaptive radiation planning for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment, while traditional response evaluation criteria inefficiently characterize tumors with complex morphological features or intrinsically low metabolism. To better assess treatment response of PA, we quantify and compare regional morphological and metabolic features of the 3D pre- and post-radiation therapy (RT) tumor models.

Materials and methods

Thirty-one PA patients with pre and post-RT Positron emission tomography/computed tomography (PET/CT) scans were evaluated. 3D meshes of pre- and post-RT tumors were generated and registered to establish vertex-wise correspondence. To assess tumor response, Mahalanobis distances (M _dist∣_Fusion) between pre- and post-RT tumor surfaces with anatomic and metabolic fused vectors were calculated for each patient. M _dist∣_Fusion was evaluated by overall survival (OS) prediction and survival risk classification. As a comparison, the same analyses were conducted on traditional imaging/physiological predictors, and distances measurements based on metabolic and morphological features only.

Results

Among all the imaging/physiological parameters, M _dist∣_Fusion was shown to be the best predictor of OS (HR = 0.52, p = 0.008), while other parameters failed to reach significance. Moreover, M _dist∣_Fusion outperformed traditional morphologic and metabolic measurements in patient risk stratification, either alone (HR = 11.51, p < 0.001) or combined with age (HR = 9.04, p < 0.001).

Conclusions

We introduced a PET/CT-based novel morphologic and metabolic pipeline for response evaluation in locally advanced PA. The fused M _dist∣_Fusion outperformed traditional morphologic, metabolic, and physiological measurements in OS prediction and risk stratification. The novel fusion model may serve as a new imaging-marker to more accurately characterize the heterogeneous tumor RT response.

Purpose

To evaluate use of breath-hold CTs and implanted fiducials for definition of the internal target volume (ITV) margin for upper abdominal stereotactic body radiation therapy (SBRT). To study the statistics of inter- and intra-fractional motion information.

Methods and materials

11 patients treated with SBRT for locally advanced pancreatic cancer (LAPC) or liver cancer were included in the study. Patients underwent fiducial implantation, free-breathing CT and breath-hold CTs at end inhalation/exhalation. All patients were planned and treated with SBRT using volumetric modulated arc therapy (VMAT). Two margin strategies were studied: Strategy I uses PTV = ITV + 3 mm; Strategy II uses PTV = GTV + 1.5 cm. Both CBCT and kV orthogonal images were taken and analyzed for setup before patient treatments. Tumor motion statistics based on skeletal registration and on fiducial registration were analyzed by fitting to Gaussian functions.

Results

All 11 patients met SBRT planning dose constraints using strategy I. Average ITV margins for the 11 patients were 2 mm RL, 6 mm AP, and 6 mm SI. Skeletal registration resulted in high probability (RL = 69%, AP = 4.6%, SI = 39%) that part of the tumor will be outside the ITV. With the 3 mm ITV expansion (Strategy 1), the probability reduced to RL 32%, AP 0.3%, SI 20% for skeletal registration; and RL 1.2%, AP 0%, SI 7% for fiducial registration. All 7 pancreatic patients and 2 liver patients failed to meet SBRT dose constraints using strategy II. The liver dose was increased by 36% for the other 2 liver patients that met the SBRT dose constraints with strategy II.

Conclusions

Image guidance matching to skeletal anatomy is inadequate for SBRT positioning in the upper abdomen and usage of fiducials is highly recommended. Even with fiducial implantation and definition of an ITV, a minimal 3 mm planning margin around the ITV is needed to accommodate intra-fractional uncertainties.

The prognosis for patients diagnosed with recurrent glioblastoma (GBM) remains poor, with no clear standard of care regarding salvage therapy. Common approaches include chemotherapy, re-resection, tumor treating fields, and reirradiation. However, most studies have shown these to have limited benefits. Reirradiation is particularly difficult due to concern for increased risk of toxicity to surrounding normal brain tissue. A novel intracranial brachytherapy system called GammaTile® (GT Medical Technologies, Tempe, Arizona) involves the placement of Cesium-131 radioactive tiles in the tumor cavity following maximal safe resection. This allows for a highly conformal dose distribution with rapid fall-off to minimize overlap with prior radiation fields and for the application of radiation directly to the high-risk tumor bed. This case report highlights a patient with GBM who survived 11.5 years through multiple recurrences and discusses the many salvage treatments he received, including bevacizumab, irinotecan, and stereotactic radiosurgery (SRS). This case exemplifies that aggressive systemic and local therapies can work well in select patients allowing for long-term survival with a good quality of life. Further efforts should be made to identify which patients may benefit from these therapies. The case study additionally reports on the use of GammaTile therapy. Due to prior external beam radiation therapy and SRS to the treatment site, further external beam radiation options were limited, and the patient was offered GammaTile as local therapy. Although it did not provide a survival benefit in this case due to progressive disease outside of the field of treatment, GammaTile serves as a valuable option in providing local therapy to patients who can no longer receive further radiation. It should be used with careful consideration in lesions characterized by aggressive local invasion.

Purpose

To apply a novel self-gating k-space sorted 4-dimensional MRI (SG-KS-4D-MRI) method to overcome limitations due to anisotropic resolution and rebinning artifacts and to monitor pancreatic tumor motion.

Methods and materials

Ten patients were imaged using 4D-CT, cine 2-dimensional MRI (2D-MRI), and the SG-KS-4D-MRI, which is a spoiled gradient recalled echo sequence with 3-dimensional radial-sampling k-space projections and 1-dimensional projection-based self-gating. Tumor volumes were defined on all phases in both 4D-MRI and 4D-CT and then compared.

Results

An isotropic resolution of 1.56 mm was achieved in the SG-KS-4D-MRI images, which showed superior soft-tissue contrast to 4D-CT and appeared to be free of stitching artifacts. The tumor motion trajectory cross-correlations (mean ± SD) between SG-KS-4D-MRI and cine 2D-MRI in superior-inferior, anterior-posterior, and medial-lateral directions were 0.93 ± 0.03, 0.83 ± 0.10, and 0.74 ± 0.18, respectively. The tumor motion trajectories cross-correlations between SG-KS-4D-MRI and 4D-CT in superior-inferior, anterior-posterior, and medial-lateral directions were 0.91 ± 0.06, 0.72 ± 0.16, and 0.44 ± 0.24, respectively. The average standard deviation of gross tumor volume calculated from the 10 breathing phases was 0.81 cm(3) and 1.02 cm(3) for SG-KS-4D-MRI and 4D-CT, respectively (P=.012).

Conclusions

A novel SG-KS-4D-MRI acquisition method capable of reconstructing rebinning artifact-free, high-resolution 4D-MRI images was used to quantify pancreas tumor motion. The resultant pancreatic tumor motion trajectories agreed well with 2D-cine-MRI and 4D-CT. The pancreatic tumor volumes shown in the different phases for the SG-KS-4D-MRI were statistically significantly more consistent than those in the 4D-CT.

Pancreatic cancer (PC) is one of the most lethal cancers, with frequent local therapy resistance and dismal 5-year survival rate. To date, surgical resection remains to be the only treatment option offering potential cure. Unfortunately, at diagnosis, the majority of patients demonstrate varying levels of vascular infiltration, which can contraindicate surgical resection. Patients unsuitable for immediate resection are further divided into locally advanced (LA) and borderline resectable (BR), with different treatment goals and therapeutic designs. Accurate definition of resectability is thus critical for PC patients, yet the existing methods to determine resectability rely on descriptive abutment to surrounding vessels rather than quantitative geometric characterization. Here, we aim to introduce a novel intra-subject object-space support-vector-machine (OsSVM) method to quantitatively characterize the degree of vascular involvement-the main factor determining the PC resectability. Intra-subject OsSVMs were applied on 107 contrast CT scans (56 LA, BR and 26 resectable (RE) PC cases) for optimized tumor-vessel separations. Nine metrics derived from OsSVM margins were calculated as indicators of the overall vascular infiltration. The combined sets of matrics selected by the elastic net yielded high classification capability between LA and BR (AUC = 0.95), as well as BR and RE (AUC = 0.98). The proposed OsSVM method may provide an improved quantitative imaging guideline to refine the PC resectability grading system.

Obesity is a known risk factor for PDA and recent reports suggest obesity has a negative impact on clinical outcomes in patients with PDA. Pretreatment body mass index (BMI) and serum albumin (SA) have been shown to be associated with worse overall survival in patients with advanced and metastatic PDA. However, minimal data exists on the impact of BMI and SA on perioperative and long-term clinical outcomes in patients with early-stage resected PDA. Herein, we report on the impact of these variables on perioperative clinical outcomes, overall survival (OS) and disease free survival (DFS) in patients with resected PDA. With IRB approval, we evaluated 1,545 patients with PDA treated at a single institution from 2007-2013 and identified 106 patients who underwent upfront resection with curative intent. BMI and SA were calculated preoperatively and at the time of last clinical evaluation. Influence of preoperative BMI, SA, change in either variable, and influence of other clinical and pathologic variables on perioperative morbidity and mortality was assessed. The impact of these variables on DFS and OS was assessed with cox regression modeling and ANOVA. Actuarial estimates for DFS and OS were calculated using Kaplan-Meier methods. Median follow up time was 16 months (3-89). Mean age was 68 years. Median survival was 14 months (3-65) and median time to recurrence was 11 months (1-79). Length of hospital stay was associated with BMI (p = .023), change in BMI (p = .003) and SA (p = .004). Post-operative transfusion rate was associated with SA (p = .021). There was a strong correlation between BMI change and positive margin (p = .04) and lymph node status (p = .01). On multivariate analysis, change in SA (p = .03) and node positivity (p = .008) were associated with decreased DFS. Additionally, preoperative SA (p = .023), node positivity (p = .026) and poor differentiation (p = .045) were associated with worse OS on multivariate analysis. Low preoperative SA was associated with worse DFS and OS in patients with resected PDA. Lower BMI and SA were associated with longer post-operative hospital stay. Our study is one of the first to describe how pre-operative BMI and SA and post-operative changes in these variables impact clinical and perioperative outcomes. This data supports nutritional status and weight loss as predictors of outcome in resected pancreatic cancer patients and warrants further prospective investigation.

Background

Pancreatic ductal adenocarcinoma has dismal prognosis. Most patients receive radiation therapy (RT), which is complicated by respiration induced organ motion in upper abdomen. The purpose of this study is to report our early clinical experience in a novel self-gated k-space sorted four-dimensional magnetic resonance imaging (4D-MRI) with slab-selective (SS) excitation to highlight tumor infiltrating blood vessels for pancreatic RT.

Methods

Ten consecutive patients with borderline resectable or locally advanced pancreatic cancer were recruited to the study. Non-contrast 4D-MRI with and without slab-selective excitation and 4D-CT with delay contrast were performed on all patients. Vessel-tissue CNR were calculated for aorta and critical vessels (superior mesenteric artery or superior mesenteric vein) encompassed by tumor. Respiratory motion trajectories for tumor, as well as involved vessels were analyzed on SS-4D-MRI. Intra-class cross correlation (ICC) between tumor volume and involved vessels were calculated.

Results

Among all 4D imaging modalities evaluated, SS-4D-MRI sampling trajectory results in images with highest vessel-tissue CNR comparing to non-slab-selective 4D-MRI and 4D-CT for all patients studied. Average (±standard deviation) CNR for involved vessels are 13.1 ± 8.4 and 3.2 ± 2.7 for SS-4D-MRI and 4D-CT, respectively. The ICC factors comparing tumor and involved vessels motion trajectories are 0.93 ± 0.10, 0.65 ± 0.31 and 0.77 ± 0.23 for superior-inferior, anterior-posterior and medial-lateral directions respectively.

Conclusions

A novel 4D-MRI sequence based on 3D-radial sampling and slab-selective excitation has been assessed for pancreatic cancer patients. The non-contrast 4D-MRI images showed significantly better contrast to noise ratio for the vessels that limit tumor resectability compared to 4D-CT with delayed contrast. The sequence has great potential in accurately defining both the tumor and boost volume margins for pancreas RT with simultaneous integrated boost.