Reconstruction of multi-phase parametric maps in 4D-magnetic resonance fingerprinting (4D-MRF) by optimization of local T1 and T2 sensitivities.

BACKGROUND: Time-resolved magnetic resonance fingerprinting (MRF), or 4D-MRF, has been demonstrated its feasibility in motion management in radiotherapy (RT). However, the prohibitive long acquisition time is one of challenges of the clinical implementation of 4D-MRF. The shortening of acquisition time causes data insufficiency in each respiratory phase, leading to poor accuracies and consistencies of the predicted tissues' properties of each phase. PURPOSE: To develop a technique for the reconstruction of multi-phase parametric maps in four-dimensional magnetic resonance fingerprinting (4D-MRF) through the optimization of local T1 and T2 sensitivities. METHODS: The proposed technique employed an iterative optimization to tailor the data arrangement of each phase by manipulation of inter-phase frames, such that the T1 and T2 sensitivities, which were quantified by the modified Minkowski distance, of the truncated signal evolution curve was maximized. The multi-phase signal evolution curves were modified by sliding window reconstruction and inter-phase frame sharing (SWIFS). Motion correction (MC) and dot product matching were sequentially performed on the modified signal evolution and dictionary to reconstruct the multi-parametric maps. The proposed technique was evaluated by numerical simulations using the extended cardiac-torso (XCAT) phantom with regular and irregular breathing patterns, and by in vivo MRF data of three health volunteers and six liver cancer patients acquired at a 3.0 T scanner. RESULTS: In simulation study, the proposed SWIFS approach achieved the overall mean absolute percentage error (MAPE) of 8.62% ± 1.59% and 16.2% ± 3.88% for the eight-phases T1 and T2 maps, respectively, in the sagittal view with irregular breathing patterns. In contrast, the overall MAPE of T1 and T2 maps generated by the conventional approach with multiple MRF repetitions were 22.1% ± 11.0% and 30.8% ± 14.9%, respectively. For in-vivo study, the predicted mean T1 and T2 of liver by the proposed SWIFS approach were 795 ms ± 38.9 ms and 58.3 ms ± 11.7 ms, respectively. CONCLUSIONS: Both simulation and in vivo results showed that the approach empowered by T1 and T2 sensitivities optimization and sliding window under the shortened acquisition of MRF had superior performance in the estimation of multi-phase T1 and T2 maps as compared to the conventional approach with oversampling of MRF data.

Dual-tracer PET/CT in the management of hepatocellular carcinoma.

Background & Aims: Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864). Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP. Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Ultra-fast multi-parametric 4D-MRI image reconstruction for real-time applications using a downsampling-invariant deformable registration (D2R) model.

BACKGROUND AND PURPOSE: Motion estimation from severely downsampled 4D-MRI is essential for real-time imaging and tumor tracking. This simulation study developed a novel deep learning model for simultaneous MR image reconstruction and motion estimation, named the Downsampling-Invariant Deformable Registration (D2R) model. MATERIALS AND METHODS: Forty-three patients undergoing radiotherapy for liver tumors were recruited for model training and internal validation. Five prospective patients from another center were recruited for external validation. Patients received 4D-MRI scans and 3D MRI scans. The 4D-MRI was retrospectively down-sampled to simulate real-time acquisition. Motion estimation was performed using the proposed D2R model. The accuracy and robustness of the proposed D2R model and baseline methods, including Demons, Elastix, the parametric total variation (pTV) algorithm, and VoxelMorph, were compared. High-quality (HQ) 4D-MR images were also constructed using the D2R model for real-time imaging feasibility verification. The image quality and motion accuracy of the constructed HQ 4D-MRI were evaluated. RESULTS: The D2R model showed significantly superior and robust registration performance than all the baseline methods at downsampling factors up to 500. HQ T1-weighted and T2-weighted 4D-MR images were also successfully constructed with significantly improved image quality, sub-voxel level motion error, and real-time efficiency. External validation demonstrated the robustness and generalizability of the technique. CONCLUSION: In this study, we developed a novel D2R model for deformation estimation of downsampled 4D-MR images. HQ 4D-MR images were successfully constructed using the D2R model. This model may expand the clinical implementation of 4D-MRI for real-time motion management during liver cancer treatment.

A dual-supervised deformation estimation model (DDEM) for constructing ultra-quality 4D-MRI based on a commercial low-quality 4D-MRI for liver cancer radiation therapy.

BACKGROUND: Most available four-dimensional (4D)-magnetic resonance imaging (MRI) techniques are limited by insufficient image quality and long acquisition times or require specially designed sequences or hardware that are not available in the clinic. These limitations have greatly hindered the clinical implementation of 4D-MRI. PURPOSE: This study aims to develop a fast ultra-quality (UQ) 4D-MRI reconstruction method using a commercially available 4D-MRI sequence and dual-supervised deformation estimation model (DDEM). METHODS: Thirty-nine patients receiving radiotherapy for liver tumors were included. Each patient was scanned using a time-resolved imaging with interleaved stochastic trajectories (TWIST)-lumetric interpolated breath-hold examination (VIBE) MRI sequence to acquire 4D-magnetic resonance (MR) images. They also received 3D T1-/T2-weighted MRI scans as prior images, and UQ 4D-MRI at any instant was considered a deformation of them. A DDEM was developed to obtain a 4D deformable vector field (DVF) from 4D-MRI data, and the prior images were deformed using this 4D-DVF to generate UQ 4D-MR images. The registration accuracies of the DDEM, VoxelMorph (normalized cross-correlation [NCC] supervised), VoxelMorph (end-to-end point error [EPE] supervised), and the parametric total variation (pTV) algorithm were compared. Tumor motion on UQ 4D-MRI was evaluated quantitatively using region of interest (ROI) tracking errors, while image quality was evaluated using the contrast-to-noise ratio (CNR), lung-liver edge sharpness, and perceptual blur metric (PBM). RESULTS: The registration accuracy of the DDEM was significantly better than those of VoxelMorph (NCC supervised), VoxelMorph (EPE supervised), and the pTV algorithm (all, p < 0.001), with an inference time of 69.3 ± 5.9 ms. UQ 4D-MRI yielded ROI tracking errors of 0.79 ± 0.65, 0.50 ± 0.55, and 0.51 ± 0.58 mm in the superior-inferior, anterior-posterior, and mid-lateral directions, respectively. From the original 4D-MRI to UQ 4D-MRI, the CNR increased from 7.25 ± 4.89 to 18.86 ± 15.81; the lung-liver edge full-width-at-half-maximum decreased from 8.22 ± 3.17 to 3.65 ± 1.66 mm in the in-plane direction and from 8.79 ± 2.78 to 5.04 ± 1.67 mm in the cross-plane direction, and the PBM decreased from 0.68 ± 0.07 to 0.38 ± 0.01. CONCLUSION: This novel DDEM method successfully generated UQ 4D-MR images based on a commercial 4D-MRI sequence. It shows great promise for improving liver tumor motion management during radiation therapy.

External Validation of a Nomogram to Predict Survival and Benefit of Concurrent Chemoradiation for Stage II Nasopharyngeal Carcinoma.

A nomogram was recently published by Sun et al. to predict overall survival (OS) and the additional benefit of concurrent chemoradiation (CCRT) vs. radiotherapy (RT) alone, in stage II NPC treated with conventional RT. We aimed to assess the predictors of OS and to externally validate the nomogram in the IMRT era. We analyzed stage II NPC patients treated with definitive RT alone or CCRT between 2001 and 2011 under the territory-wide Hong Kong NPC Study Group 1301 study. Clinical parameters were studied using the Cox proportional hazards model to estimate OS. The nomogram by Sun et al. was applied with 1000 times bootstrap resampling to calculate the concordance index, and we compared the nomogram predicted and observed 5-year OS. There were 482 patients included. The 5-year OS was 89.0%. In the multivariable analysis, an age > 45 years was the only significant predictor of OS (HR, 1.98; 95%CI, 1.15-3.44). Other clinical parameters were insignificant, including the use of CCRT (HR, 0.99; 95%CI, 0.62-1.58). The nomogram yielded a concordance index of 0.55 (95% CI, 0.49-0.62) which lacked clinically meaningful discriminative power. The nomogram proposed by Sun et al. should be interpreted with caution when applied to stage II NPC patients in the IMRT era. The benefit of CCRT remained controversial.

Factors correlating with shorter survival after treatment: aiding oncologists to choose who (not) to receive palliative systemic therapy.

BACKGROUND: A rising number of metastatic cancer patients are receiving palliative systemic therapy close to end of life. Patients started on such treatment are typically judged by oncologists to have at least 12 weeks survival, however, accurate survival prediction on individual patients is difficult. Systemic therapy started too late may not benefit patient, but rather, adversely affect patient's quality of life and may even shorten survival due to treatment-related side effects. Our objective is to identify factors correlating with a shorter (≤6 weeks) non-malignancy related survival in metastatic cancer patients receiving palliative systemic therapy, so as to aid oncologist in the decision-making of starting treatment or not. METHODS: A review of deceased metastatic cancer patients treated with palliative systemic therapy and died between January 2013 and December 2014 was carried out. They were subcategorized into dying within or after 6 weeks since starting their last line of palliative systemic therapy, and also by cause of death (malignancy-related or non-malignancy related causes). Demographics, clinical characteristics, and type of systemic therapy used were assessed using non-parametric Mann Whitney-U tests for continuous variables and χ2 tests for categorical variables. Univariable analyses were carried out to determine associations of different variables with non-malignancy related death that happened within 6 weeks of starting their last line of palliative systemic therapy. Multivariable analyses were carried out with significant factors in univariable analyses to determine their independent effect. RESULTS: Seven hundred and fifty-four patients were analyzed. Mean age was 63.6 (range, 21-102); female 48.7%. Older age (75 years) (P=0.007) and active liver metastasis (P=0.042) were significant predictors for early (≤6 weeks) non-malignancy related death in multivariable analysis. They have 2.012 and 1.115 times higher chance respectively to die of non-malignant causes within 6 weeks since the start of their last line of palliative systemic treatment. CONCLUSIONS: Oncologists should exercise extra caution when encountering elderly patients with active liver metastasis, especially with regard to the issue of starting palliative systemic therapy.

Revisiting oral fluoropyrimidine with cetuximab in metastatic colorectal cancer: Real-world data in Chinese population.

BACKGROUND: Cetuximab in combination with oral fluoropyrimidine (FP) remains controversial in metastatic colorectal cancer (mCRC). In view of the regional variation in the tolerability of FP, we conducted a retrospective analysis to compare oral FP with infusional FP in combination with cetuximab in Chinese population. AIM: To compare the efficacy and safety profile of cetuximab in combination with oral FP and infusional FP in Chinese population in the real-world setting. METHODS: A retrospective cohort study was done to analyse consecutive patients with Kras wild-type mCRC who received first-line treatment with cetuximab and FP-based chemotherapy in our unit from January 2010 to December 2015. Ninety-five eligible patients were included. The median follow-up of our cohort was 65.0 mo. RESULTS: The median progression-free survival (mPFS) and median overall survival (mOS) of the entire cohort were 9.66 mo (95%CI: 7.72-12.5) and 25.8 mo (95%CI: 18.7-35.6), respectively. Between oral FP and infusional FP, there was no statistical significant difference in the mPFS [9.79 mo (95%CI: 7.49-12.7) vs 9.63 mo (95%CI: 6.34-13.4); P = 0.72] and mOS [25.8 mo (95%CI: 15.2-35.6) vs 26.3 mo (95%CI: 18.7-41.2); P = 0.63]. Grade 3 or above adverse events were reported in 28.4% of patients, being similar with oral and infusional FP, and included 10.5% of neutropenia and 2.1% of diarrhoea events. CONCLUSION: The current analysis demonstrates comparable efficacy and safety profiles of cetuximab in combination with oral and infusional FP in Chinese population. The results expand treatment options for Chinese patients and invite revision of existing treatment guidelines to incorporate oral FP-based chemotherapy plus cetuximab.

Effect of YH0618 soup on chemotherapy-induced toxicity in patients with cancer who have completed chemotherapy: study protocol for a randomized controlled trial.

BACKGROUND: The incidence of cancer has been staying at a high level worldwide in recent years. With advances in cancer diagnosis and therapy strategy, the survival rate of patients with cancer has been increasing, but the side effects of these treatments, especially chemotherapy, are obvious even when the chemotherapy ceases. YH0618, a prescription, has showed efficacy in reducing chemotherapy-induced toxicity through long clinical practice. However, there is no scientific research exploring the effects of YH0618 in patients with cancer. Therefore, using a randomized controlled trial, this study will explore the efficacy of YH0618 on ameliorating chemotherapy-induced toxicity including dermatologic toxicity, myelosuppression, hepatotoxicity and nephrotoxicity and improving fatigue in cancer patients who have completed chemotherapy. METHODS/DESIGN: This is a prospective assessor-blinded, parallel, randomized controlled trial. Patients with cancer at any stage who have completed chemotherapy within two weeks will be randomly divided into group A (YH0618) and group B (wait-list) using a 1:1 allocation ratio. The chemotherapeutic agents include taxanes or anthracyclines. Subjects assigned to group A will receive YH0618 soup 6 days a week for 6 weeks and uncontrolled follow-up for 6 weeks, while group B are required to wait for 6 weeks before receiving YH0618 intervention. The primary outcome of this study is the incidence of protocol-specified grade ≥2 dermatologic toxicities graded by NCI CTCAE Chinese version 4.0 and changes of fingernail color, face skin color and tongue color evaluated by the L*a*b system within 6 weeks. There are some secondary outcomes associated with dermatologic toxicity including fatigue and clinical objective examination. DISCUSSION: There are few scientific and safe methods in ameliorating chemotherapy-induced toxicity. The proposed study may provide direct and convincing evidence to support YH0618 as an adjuvant treatment for reducing chemotherapy-induced toxicity, which could be introduced into clinical settings. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-IOR-15006486 . Registered on 21 May 2015.

Correlation of measurements from diffusion weighted MR imaging and FDG PET/CT in GIST patients: ADC versus SUV.

PURPOSE: We investigated the correlation relationship between ADCs measured by MRI and SUVs measured by PET/CT of lesions on GIST (gastrointestinal stromal tumor) patients to verify if MR is able to replace or serve as an alternative to PET/CT in GIST staging and treatment monitoring. MATERIALS AND METHODS: Between September 2010 and January 2011, five patients with histologically proven metastatic GIST in Queen Mary Hospital, Hong Kong were enrolled into our study. All patients underwent both MRI and PET/CT scans at prognosis. Pearson's correlations of twenty-nine lesions were conducted between 5 pairs of ADCs and SUVs values. RESULTS: Lesions in the liver, peritoneum or bowel loops were found by PET/CT and no extra-abdominal lesion was identified. All twenty-nine lesions are identifiable by MRI with sensitivity of 100%. Significant inverse correlation were found between ADC(mean) and SUV(mean) (P=0.006), ADC(mean) and SUV(max) (P=0.010), ADC(min) and SUV(max) (P=0.014), ADC(min) and SUV(mean) (P=0.026), rADC(min) and rSUV(max) (P=0.047). CONCLUSION: DWI is comparable to PET/CT in visually detecting the GIST lesions' location. Significant inverse correlations were found between ADCs from DWIBS and SUVs from PET/CT on data of GIST patients. This finding demonstrates that DWI is potentially capable of offering similar information for diagnosis and treatment response evaluating in GIST's patients as PET/CT does. Furthermore, ADC(min), which is determined by single pixel, is not as reliable as ADC(mean), which is weighted average value of the whole lesion volume.