A.L.H.M.W. Van Lier

7-T 1H MRS with adiabatic refocusing at short TE using radiofrequency focusing with a dual-channel volume transmit coil

In vivo MRS of the human brain at ultrahigh field allows for the identification of a large number of metabolites at higher spatial resolutions than currently possible in clinical practice. However, the in vivo localization of single‐voxel spectroscopy has been shown to be challenging at ultrahigh field because of the low bandwidth of refocusing radiofrequency (RF) pulses. Thus far, the proposed methods for localized MRS at 7 T suffer from long TE, inherent signal loss and/or a large chemical shift displacement artifact that causes a spatial displacement between resonances, and results in a decreased efficiency in editing sequences. In this work, we show that, by driving a standard volume coil with two RF amplifiers, focusing the B  1+ field in a certain location and using high‐bandwidth adiabatic refocusing pulses, a semi‐LASER (semi‐localized by adiabatic selective refocusing) localization is feasible at short TE in the human brain with full signal acquisition and a low chemical shift displacement artifact at 7 T. Copyright

Imaging of oesophageal cancer with FDG-PET/CT and MRI

Integrated 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) PET/CT and magnetic resonance imaging (MRI) with functional features of diffusion-weighted imaging (DWI) are advancing imaging technologies that have current and future potential to overcome important limitations of conventional staging methods in the management of patients with oesophageal cancer. PET/CT has emerged as an important part of the standard work-up of patients with oesophageal cancer. Besides its important ability to detect unsuspected metastatic disease, PET/CT may be useful in the assessment of treatment response, radiation treatment planning, and detection of recurrent disease. In addition, high-resolution T2-weighted MRI and DWI have potential complementary roles. Recent improvements in MRI protocols and techniques have resulted in better imaging quality with the potential to bring improvement in staging, radiation treatment planning, and the assessment of treatment response. Optimal use and understanding of PET/CT and MRI in oesophageal cancer will contribute to the impact of these advancing technologies in tailoring treatment to the individual patient and achieving best possible outcomes. In this article, we graphically outline the current and potential future roles of PET/CT and MRI in the multidisciplinary management of oesophageal cancer.

In vivo electric conductivity of cervical cancer patients based on B₁⁺ maps at 3T MRI.

The in vivo electric conductivity (σ) values of tissue are essential for accurate electromagnetic simulations and specific absorption rate (SAR) assessment for applications such as thermal dose computations in hyperthermia. Currently used σ-values are mostly based on ex vivo measurements. In this study the conductivity of human muscle, bladder content and cervical tumors is acquired non-invasively in vivo using MRI. The conductivity of 20 cervical cancer patients was measured with the MR-based electric properties tomography method on a standard 3T MRI system. The average in vivo σ-value of muscle is 14% higher than currently used in human simulation models. The σ-value of bladder content is an order of magnitude higher than the value for bladder wall tissue that is used for the complete bladder in many models. Our findings are confirmed by various in vivo animal studies from the literature. In cervical tumors, the observed average conductivity was 13% higher than the literature value reported for cervical tissue. Considerable deviations were found for the electrical conductivity observed in this study and the commonly used values for SAR assessment, emphasizing the importance of acquiring in vivo conductivity for more accurate SAR assessment in various applications.

The peri‐esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri‐esophageal fascias have not been described and it is unclear whether this layer can be visualized by non‐invasive imaging. This study aimed to provide a comprehensive description of the peri‐esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2‐weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri‐esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion‐triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named ‘aorto‐esophageal ligament’ and the layer connecting aorta to the right pleural reflection ‘aorto‐pleural ligament’. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named ‘peri‐esophageal compartment’ and the posterior compartment ‘para‐aortic compartment’. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long‐standing paradigm that no such structure exists. A comprehensive, detailed description of the peri‐esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI.

CSI-EPT: A novel contrast source approach to MRI based electric properties tomography and patient-specific SAR

In this paper, we present a novel method (Contrast Source Inversion - Electric Properties Tomography or CSI-EPT) to dielectric imaging of biological tissue using so-called B1+ data measurable by Magnetic Resonance Imaging (MRI) systems. Integral representations for the electromagnetic field quantities are taken as a starting point and we follow an iterative contrast source inversion approach to retrieve the dielectric tissue parameters from measured field data. Numerical results illustrate the performance of the method and show that reliable results are produced near tissue boundaries as opposed to the currently used methods. Fine structures can be resolved as well and since CSI-EPT reconstructs the electric field strength inside a scanning region of interest, it is also a promising candidate to determine the patient-specific SAR deposition during an MRI scan.

SU‐E‐J‐57: MRI‐Linac (MRL) Guided Treatment for Esophageal Cancer

For radiotherapy, oesophageal cancer is located in a difficult area. Spatial control of the dose distribution is difficult to achieve with current CT-based radiation techniques, as on CT, soft-tissue contrast is too low. Furthermore, the oesophagus moves and organs at risk (e.g. lung, heart, liver, spinal cord) are in close proximity. An 1.5 T MRI-accelerator (MRL) has sufficient soft-tissue tumour visualization possibilities to allow for precise real-time, online, position verification and for dose escalation without organ at riskoverdose. Our research consists of the preparatory work for the first clinical study on the MRL for patients with oesophageal cancer. To improve image quality and reduce the motion artefacts, the benefit of cardiac triggering and breath holds is evaluated on fifteen oesophageal patients. Results show the superb image quality of these MRI sequences. The use of this high quality MRI gives the possibility for non-invasive real-time visualization andtracking of the tumour. We quantify oesophageal tumour motion on cineMRI. The tumour is tracked on sequential mixed T1/T2w images (acquisition time: 60s, temporal resolution: 0.5s, slice thickness: 7mm) of a single coronal and sagittal slice using a Minimum Output Sum of Squared Error (MOSSE) adaptive correlation filter. Tumour registration within the individual images can typically be done at a millisecond time scale. Motion of oesophageal tumours can well be tracked and is highly variable between patients. The greatest mobility is seen in cranio-caudal direction, with amaximum peak-to-peak amplitude of tumour movement of 24.5mm followed by the dorso-ventral and the medio-lateral direction. Movement seems greatest in tumours located in the lower part of the oesophagus. This study shows both the superb image quality for GTV localisation and the possibility for on-line and real time tumour tracking. The study opens thepossibility for tracked radiation delivery with a 1.5T MRI accelerator. Partial funding has been obtained by Elekta and Philips.

Gross tumour delineation on Computed Tomography and Positron Emission Tomography-Computed Tomography in oesophageal cancer: a nationwide study

Background and purpose Accurate delineation of the primary tumour is vital to the success of radiotherapy and even more important for successful boost strategies, aiming for improved local control in oesophageal cancer patients. Therefore, the aim was to assess delineation variability of the gross tumour volume (GTV) between CT and combined PET-CT in oesophageal cancer patients in a multi-institutional study. Materials and methods Twenty observers from 14 institutes delineated the primary tumour of 6 cases on CT and PET-CT fusion. The delineated volumes, generalized conformity index (CIgen) and standard deviation (SD) in position of the most cranial/caudal slice over the observers were evaluated. For the central delineated region, perpendicular distance between median surface GTV and each individual GTV was evaluated as in-slice SD. Results After addition of PET, mean GTVs were significantly smaller in 3 cases and larger in 1 case. No difference in CIgen was observed (average 0.67 on CT, 0.69 on PET-CT). On CT cranial-caudal delineation variation ranged between 0.2 and 1.5 cm SD versus 0.2 and 1.3 cm SD on PET-CT. After addition of PET, the cranial and caudal variation was significantly reduced in 1 and 2 cases, respectively. The in-slice SD was on average 0.16 cm in both phases. Conclusion In some cases considerable GTV delineation variability was observed at the cranial-caudal border. PET significantly influenced the delineated volume in four out of six cases, however its impact on observer variation was limited.

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study

BackgroundNearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR.MethodsThe PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival.DiscussionIf the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped.Trial registrationThe article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341.

WE‐G‐18C‐04: Comparison of Image Registration Strategies to Improve DCE‐MRI Uptake Curves in Esophageal Cancer

PURPOSE Neoadjuvant chemoradiotherapy (nCRT) is often used to treat resectable esophageal cancer. In 29% of the patients, nCRT results in a pathologic complete reponse (pCR). pCR is an important prognostic factor and surgery can potentially be omitted in this patient group. We will study the potential of DCE-MRI for accurate response assessment in those patients. In preparation to this study, motion compensation by retrospective image registration strategies of DCE-MRI time series was investigated to enable correct pharmacokinetic analysis required for response assessment. METHODS Five patients with biopsy-proven esophageal cancer received a DCE-MRI scan (62 time-frames, 3 s/frame) prior to neoadjuvant therapy; contrast was injected after the 10th time-frame. Three different registration strategies were reviewed; registration to: (1) 1st time-frame, (2) 41th timeframe, and (3) previous time-frame; rigid or affine transformations were allowed (using Elastix toolbox). We chose these time-points as they occur well before (1) or after (2) contrast uptake. In strategy (3), the registration process is thought to be less susceptible to image intensity variations caused by contrast uptake. The effectiveness of the registration strategies was measured with SSIM (structure component of Structural SIMilarity, 1 = perfect match) metric within the volume encompassing the tumor. The 41th frame was chosen as reference image. RESULTS The average SSIM over all time-frames and patients was: pre-registration: 0.67, post-registration rigid to 1st/41th/previous frame: 0.68/0.70/0.66, affine: 0.68/0.69/0.66. For rigid registration to frame 41, the minimum and maximum SSIM change per time-frame ranged from -0.09 to 0.14. CONCLUSION In this analysis, rigid registration to a time-frame after contrast-enhancement led to the best retrospective motion compensation of DCE-MRI in esophageal cancer measured by SSIM. After verification in a larger patient group, this correction will be used prior to semi-quantitative analysis and pharmacokinetic modeling to assess response to neoadjuvant therapy.

TU-C-12A-03: Functional MRI of Esophageal Cancer: Repeatability and Inter-Observer Reproducibility of Geometrically Corrected ADC Maps

PURPOSE In preparation to treatment response monitoring with diffusion weighted imaging (DWI) of neoadjuvant chemoradiation of esophageal cancer, we determined the repeatability and inter-observer reproducibility of the apparent diffusion coefficient (ADC). Geometrical corrections were performed prior to analysis, to enable multi-parametric analysis on the same ROI. METHODS Ten patients with biopsy-proven esophageal cancer underwent an MRI exam before, during and after neoadjuvant chemoradiotherapy. The scan protocol consisted of an anatomical T2w scan (TE/TR = 100/1938ms), a DWI scan (b = 0, 200, 800 s/mm2 , voxel size 3.25×3.25mm) and a B0 map to monitor magnetic field distortions (dual echo, dual acquisition, TE1/TE2 = 4.6/9.2ms). DWI scans were obtained with a single shot echo-planar read-out (BW_phaseenc ∼ 30 Hz/pixel). Two acquisitions were performed with opposing phase-encoding gradient directions, which results in opposing geometrical distortions. Subsequently, both DWI scans were geometrically corrected using the B0 map, and ADC maps were calculated. For analysis of the inter-observer reproducibility, two clinicians delineated the tumor volume on the T2w image. The ROIs were transferred to the ADC map. Finally, the repeatability was determined by comparing the ADC within one ROI between the two DWI scans in an exam. The inter-observer reproducibility was determined by comparing the ADC values within the two ROIs. RESULTS The average geometrical distortion over all ROIs was 2.67mm (range: 0.02-17.66mm). The repeatability of geometrical corrected ADC maps was 10.0%, the inter-observer reproducibility 7.9%. Both percentages are 95%-confidence intervals (1.96x standard deviation of median ADC). CONCLUSION Geometrical correction was required as considerable distortions were observed. Corrected ADC maps of esophageal cancer are associated with a modest repeatability error and inter-observer reproducibility error, which are in the same range compared to previous reports in other malignancies. In future, we will incorporate repeatability and reproducibility data in MRI-based (multi-parametric) treatment response models of esophageal cancer.