Variable Contrast Enhancement Research Articles

Notochordal cell derived lesions: a 55-year casuistic analysis of 50 cases with radiologic-pathologic correlation in a tertiary referral hospital, and literature review.

Distinct lesions are derived from notochordal cells (NCDL), ranging from benign to malignant ones. This study presents fifty NCDL cases diagnosed in a tertiary hospital of reference from the past 55 years: forty-two conventional chordomas, including one chondroid chordoma subtype, four benign notochordal cell tumors (BNCT), two conventional chordomas with BNCT foci, and two dedifferentiated chordomas. All patients were adults. Three BNCT were incidentally diagnosed, and one case presented local pain. Chordomas began with local pain and/or neurological symptoms. BNCT were well-defined intraosseous lesions, hypointense on T1-weighted images (WI) and hyperintense on T2-WI, without enhancement in the contrast. Conventional chordomas, including its chondroid subtype, were lobulated masses with cortical disruption and soft tissue extension, hypointense on T1-WI and hyperintense on T2-WI, with variable contrast enhancement. BNCT were histologically composed of solid sheets of vacuolated cells with clear cytoplasm and round and central nuclei. No atypia, lobular growth pattern, myxoid matrix, or bone infiltration were seen. Conventional chordomas were histologically composed of physaliphorous cells in a myxoid stroma with lobulated and infiltrating growth patterns. Observational follow-up using radiological controls was decided on for the BNCT cases. None of these cases presented local recurrence or metastasis. En-bloc resection and adjuvant radiotherapy were selected for sacral and vertebral chordoma cases. Sixteen patients died due to tumor-related factors; twenty-eight presented local recurrence, and four developed distant metastases. New therapeutic options are being studied for chordoma cases. Clinical, radiological, and histopathological data are necessary to properly diagnose and follow up of NCDL.

How can we differentiate supratentorial tumor recurrence from postradiation imaging changes in children treated for primary malignant brain tumors?

Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence. The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated. The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up. MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.

MRI ischemic and hemorrhagic lesions in arterial and venous territories characterize central nervous system intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

Non-enhancing intraventricular tumours in adults.

Intraventricular tumours are relatively uncommon among all brain tumours, and non-enhancing lesions, mostly subependymoma, are even less frequently reported. Select cases of subependymoma can show variable contrast enhancement as well. Gross total surgical resection is recommended for treating these lesions, with no significant role of adjuvant chemotherapy or radiotherapy.

Fluorine‐18 fluorodeoxyglucose positron emission tomography‐computed tomography for staging of canine insulinoma: 3 cases (2019–2020)

Canine insulinomas are uncommon malignant functional pancreatic neuroendocrine tumours with a high metastatic rate. Diagnostic imaging aids with staging and surgical planning of these tumours; however, identification is unpredictable across modalities. High-grade human pancreatic neuroendocrine tumours display increased avidity on 18 F-fluorodeoxyglucose positron emission tomography-CT. Dogs with clinicopathologic findings consistent with pancreatic insulinoma were prospectively enrolled. Patients underwent 18 F-fluorodeoxyglucose positron emission tomography-CT and CT angiography, followed by exploratory laparotomy. Three patients met the inclusion criteria and had histologically confirmed insulinomas. Both metastatic lesions in patient 1 were mildly avid (SUVmax 2.79 and 3.01). In patient 2, the primary pancreatic insulinoma was minimally avid (SUVmax 2.16). The primary pancreatic lesion in patient 3 had similar avidity to normal pancreatic parenchyma (SUVmax 1.54) and was undetected on 18 F-fluorodeoxyglucose positron emission tomography-CT. Insulinomas demonstrated variable attenuation and contrast enhancement patterns on CT angiography and certain lesions were more conspicuous than on 18 F-fluorodeoxyglucose positron emission tomography-CT. Two metastatic lesions not visible on either imaging modality were discovered in patient 2 at surgery. Canine insulinomas were inconsistently avid on 18 F-fluorodeoxyglucose positron emission tomography-CT. This finding is likely attributable to the confounding clinicopathological features and multifaceted transformation of these tumours, in addition to the influence of variable tumour size, composition and vascularity. Unpredictable tumoural avidity limits the value of 18 F-fluorodeoxyglucose positron emission tomography-CT for staging canine insulinomas.

IMG-12. CHARACTERISATION OF MODELS OF H3F3A_G34R/V MUTANT PAEDIATRIC GLIOBLASTOMA IN VIVO USING MAGNETIC RESONANCE IMAGING

Approximately 15% of paediatric/young adult cerebral hemispheric glioblastomas (pGBM) harbour G34R/V mutations in H3F3A, encoding the histone H3.3 variant. Development of novel therapeutic interventions demands models that accurately recapitulate this subset of disease and sensitive imaging methods with which to study tumours in situ. Three H3F3A_G34R primary-patient-derived cultures, alongside established cell-line KNS42 (H3F3A_G34V), were implanted orthotopically in immunocompromised mice. KNS42 (TP53_R342*) tumours were clearly detectable using T2-weighted (T2w)-MRI, enhanced following contrast agent administration, indicating impaired blood-brain barrier (BBB) integrity, and demonstrated minimal invasion. OPBG_GBM_001 cells (TP53_89-90X,ATRX_II2133-2144X) formed infiltrative tumours that were hyperintense on T2w-MRI and demonstrated contrast-enhancement suggestive of heterogeneous BBB integrity. HSJD_GBM_002 cells (TP53_P278T,ATRX_R666*) spread diffusely throughout the brain with their full extent typically not discernible by T2w-MRI, the BBB also remaining intact. No evidence of CHOP_GBM_001 tumour was detected by MRI 11months post-implantation. Immunocompetent syngeneic models using tumour cells induced by mutations modelling hemispheric pGBM (NRAS/shP53/shATRX±H3.3G34R) are being explored. Fast growing heterogeneous lesions with variable contrast-enhancement were identified; the H3.3G34R mutation conferred longer median survival (2 clones:25/28days, control:14days). These models have the advantage of an intact immune system and short latency for initial efficacy studies. Primary pGBM cells yield tumours that are more representative of the spectrum of clinical disease; variable hyperintensity on T2w-MRI corresponding to cellular density, with diffusely infiltrative disease less clearly definable, a paucity of oedema and a range of contrast-enhancement. Pathological features including giant multinucleated cells, and mitotic figures were also evident.

Characterization of Liver Metastases During Catheter-Directed Liver Interventions: A Comparison between Dual Phase Cone-Beam Computed Tomography and Conventional Contrast-Enhanced Computed Tomography.

Objectives:To compare the diagnostic performance of intra-arterial dual phase cone-beam computed tomography (DP-CBCT) with contrast-enhanced computed tomography (CE-CT) when characterizing tumor burden in patients with metastatic liver cancer.Materials and Methods:This retrospective study included 29 patients with colorectal (n =10), breast (n = 9) and neuroendocrine (n = 10) liver metastases, referred for catheter-directed treatment. Tumor type, number, maximum size, and appearance were assessed. Paired-sample t-tests compared image quality, tumor numbers, and diameters between imaging modalities.Results:Image quality was not different between DP-CBCT and CE-CT (p = 0.9). In 18 patients (62%) DP-CBCT and CE-CT showed diffuse, uncountable metastases in the liver. Of the remaining 11 patients, DP-CBCT identified two patients with diffuse tumors that appeared as a sum of 17 distinct metastases on CE-CT. In the remaining nine patients a total of 102 metastases were found using both DP-CBCT and CE-CT. Tumor detection accuracy was 98% in DP-CBCT and 67% in CE-CT (p = 0.025). Metastases were larger in diameter on DP-CBCT: colorectal: 57 +/– 9.5 mm versus 43 +/– 8.3 mm (p = 0.02); breast: 57 +/– 10 mm versus 43 +/– 8.5 mm (p = 0.03) and neuroendocrine: 56 +/– 6.3 mm versus 51 +/– 5.8 mm (p = 0.01). Rim enhancement appeared in 100% of patients with colorectal and 89% of patients with breast metastases on DP-CBCT, but was variable on CE-CT. Neuroendocrine tumors had variable rim enhancement within the same patient and across imaging modalities.Conclusions:DP-CBCT of the liver may demonstrate larger metastatic tumor burden and lesion size with a variable contrast enhancement compared to CE-CT.

Radiomics-Based Prediction of Long-Term Treatment Response of Vestibular Schwannomas Following Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) is one of the treatment modalities for vestibular schwannomas (VSs). However, tumor progression can still occur after treatment. Currently, it remains unknown how to predict long-term SRS treatment outcome. This study investigates possible magnetic resonance imaging (MRI)-based predictors of long-term tumor control following SRS. Retrospective cohort study. Tertiary referral center. Analysis was performed on a database containing 735 patients with unilateral VS, treated with SRS between June 2002 and December 2014. Using strict volumetric criteria for long-term tumor control and tumor progression, a total of 85 patients were included for tumor texture analysis. All patients underwent SRS and had at least 2 years of follow-up. Quantitative tumor texture features were extracted from conventional MRI scans. These features were supplied to a machine learning stage to train prediction models. Prediction accuracy, sensitivity, specificity, and area under the receiver operating curve (AUC) are evaluated. Gray-level co-occurrence matrices, which capture statistics from specific MRI tumor texture features, obtained the best prediction scores: 0.77 accuracy, 0.71 sensitivity, 0.83 specificity, and 0.93 AUC. These prediction scores further improved to 0.83, 0.83, 0.82, and 0.99, respectively, for tumors larger than 5 cm. Results of this study show the feasibility of predicting the long-term SRS treatment response of VS tumors on an individual basis, using MRI-based tumor texture features. These results can be exploited for further research into creating a clinical decision support system, facilitating physicians, and patients to select a personalized optimal treatment strategy.

Coil embolisation of post traumatic giant supraclinoid pseudoaneurysm presenting as carotid cavernous fistula

This report documents the occurrence, diagnosis and treatment of a 29 year-old male patient who presented with progressive swelling of the left eye with associated progressive loss of vision, three months after sustaining a closed head injury in a road traffic accident. Magnetic resonance imaging (MRI) showed a large, ill-defined lesion in the left supraclinoid and paraclinoid region with variable contrast enhancement. A four vessel Digital Subtraction Angiography (DSA) showed a large, supra-clinoid pseudoaneurysm which had ruptured inferiorly into the roof of cavernous sinus, forming direct carotid cavernous fistula (CCF) which lead to dilatation of the superior ophthalmic vein and subsequent peri-orbital oedema and chemosis of conjunctiva. Complete obliteration of the indirect CCF was achieved by coiling of the aneurysm alone. During follow up, patient reported a significant improvement in vision and follow up DSA after one year shows no recurrence with this technique.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

The secondary spiral lamina and its relevance in cochlear implant surgery

Objective: We used synchrotron radiation phase contrast imaging (SR-PCI) to study the 3D microanatomy of the basilar membrane (BM) and its attachment to the spiral ligament (SL) (with a conceivable secondary spiral lamina [SSL] or secondary spiral plate) at the round window membrane (RWM) in the human cochlea. The conception of this complex anatomy may be essential for accomplishing structural preservation at cochlear implant surgery.Material and methods: Sixteen freshly fixed human temporal bones were used to reproduce the BM, SL, primary and secondary osseous spiral laminae (OSL), and RWM using volume-rendering software. Confocal microscopy immunohistochemistry (IHC) was performed to analyze the molecular constituents.Results: SR-PCI reproduced the soft tissues including the RWM, Reissner’s membrane (RM), and the BM attachment to the lateral wall (LW) in three dimensions. A variable SR-PCI contrast enhancement was recognized in the caudal part of the SL facing the scala tympani (ST). It seemed to represent a SSL allied to the basilar crest (BC). The SSL extended along the postero-superior margin of the round window (RW) and immunohistochemically expressed type II collagen.Conclusions: Unlike in several mammalian species, the human SSL is restricted to the most basal portion of the cochlea around the RW. It anchors the BM and may influence its hydro-mechanical properties. It could also help to shield the BM from the RW. The microanatomy should be considered at cochlear implant surgery.

Canine spinal cord glioma

Spinal cord glioma is uncommonly reported in dogs. We describe the clinicopathologic and diagnostic features of 7 cases of canine spinal cord glioma and briefly review the veterinary literature on this topic. The median age at presentation was 7.2 y. Six females and 1 male were affected and 4 dogs were brachycephalic. The clinical course lasted from 3 d to 12 wk, and clinical signs were progressive and associated with multiple suspected neuroanatomic locations in the spinal cord. Magnetic resonance imaging of 6 cases revealed T2-weighted hyperintense lesions with variable contrast enhancement in the spinal cord. All dogs had a presumptive clinical diagnosis of intraparenchymal neoplasia or myelitis based on history, advanced imaging, and cerebrospinal fluid analysis. Euthanasia was elected in all cases because of poor outcome despite anti-inflammatory or immunosuppressive treatment or because of poor prognosis at the time of diagnosis. Tumor location during autopsy ranged from C1 to L6, with no clear predilection for a specific spinal cord segment. The diagnosis was based on histopathology and the immunohistochemistry expression of glial fibrillary acidic protein, oligodendrocyte lineage transcription factor 2, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, neuron-specific enolase, synaptophysin, and Ki-67. Diagnoses consisted of 4 cases of oligodendroglioma, 2 cases of gliomatosis cerebri, and 1 astrocytoma. This case series further defines the clinicopathologic features of canine spinal glioma and highlights the need for comprehensive immunohistochemistry in addition to routine histopathology to confirm the diagnosis of these tumors.

Logarithmic intensity compression in fluorescence guided surgery applications.

The use of fluorescence video imaging to guide surgery is rapidly expanding, and improvements in camera readout dynamic range have not matched display capabilities. Logarithmic intensity compression is a fast, single-step mapping technique that can map the useable dynamic range of high-bit fluorescence images onto the typical 8-bit display and potentially be a variable dynamic contrast enhancement tool. We demonstrate a ∼4.6 times improvement in image quality quantified by image entropy and a dynamic range reduction by a factor of ∼380 by the use of log-compression tools in processing in vivo fluorescence images.

Biphasic Pulmonary Blastoma: a Case Report and Literature Review

Introduction: Biphasic Pulmonary blastoma (BPB) is classified as one of the rare primary lung malignancies. It is composed of a mixture of epithelial and mesenchymal tissues resembling embryonic lung tissue. BPB is considered to be distinct from other lung tumors based on pathological features, clinical course and prognosis. Presentation of Case: The authors report an atypical case of BPB in a 27 -year-old man presented with complaints of dyspnea and left-sided chest pain for the previous four months. A chest radiograph showed the presence of an opaque left hemithorax, and the mediastinum was pushed toward the left. Computed tomography (CT) of the chest revealed a mixed solid and cystic process with variable contrast enhancement measuring 15,4 x 13,7 cm occupying the totality of the left hemithorax, pleural effusion, and a collapsed left lung, with contralateral mediastinal shift. A transthoracic needle pleural biopsy yielded a diagnosis of BPB.A general examination shows a peritoneal effusion. One month after diagnosis, the tumor grew rapidly, and therefore he was treated only by palliative care. He died from respiratory failure one month later. Although BPB is rare, this entity is increasingly described.

A framework for deformable image registration validation in radiotherapy clinical applications.

Quantitative validation of deformable image registration (DIR) algorithms is extremely difficult because of the complexity involved in constructing a deformable phantom that can duplicate various clinical scenarios. The purpose of this study is to describe a framework to test the accuracy of DIR based on computational modeling and evaluating using inverse consistency and other methods. Three clinically relevant organ deformations were created in prostate (distended rectum and rectal gas), head and neck (large neck flexion), and lung (inhale and exhale lung volumes with variable contrast enhancement) study sets. DIR was performed using both B‐spline and diffeomorphic demons algorithms in the forward and inverse direction. A compositive accumulation of forward and inverse deformation vector fields was done to quantify the inverse consistency error (ICE). The anatomical correspondence of tumor and organs at risk was quantified by comparing the original RT structures with those obtained after DIR. Further, the physical characteristics of the deformation field, namely the Jacobian and harmonic energy, were computed to quantify the preservation of image topology and regularity of spatial transformation obtained in DIR. The ICE was comparable in prostate case but the B‐spline algorithm had significantly better anatomical correspondence for rectum and prostate than diffeomorphic demons algorithm. The ICE was 6.5 mm for demons algorithm for head and neck case when compared to 0.7 mm for B‐spline. Since the induced neck flexion was large, the average Dice similarity coefficient between both algorithms was only 0.87, 0.52, 0.81, and 0.67 for tumor, cord, parotids, and mandible, respectively. The B‐spline algorithm accurately estimated deformations between images with variable contrast in our lung study, while diffeomorphic demons algorithm led to gross errors on structures affected by contrast variation. The proposed framework offers the application of known deformations on any image datasets, to evaluate the overall accuracy and limitations of a DIR algorithm used in radiation oncology. The evaluation based on anatomical correspondence, physical characteristics of deformation field, and image characteristics can facilitate DIR verification with the ultimate goal of implementing adaptive radiotherapy. The suitability of application of a particular evaluation metric in validating DIR is dependent on the clinical deformation observed.PACS numbers: 87.57 nj, 87.55‐x,87.55 Qr

From the Radiologic Pathology Archives: Cardiac Lymphoma: Radiologic-Pathologic Correlation

Lymphoma of the heart and pericardium is usually present as one aspect of disseminated disease and rarely occurs as a primary malignancy. It accounts for 1.3% of primary cardiac tumors and 0.5% of extranodal lymphomas. Cardiac lymphomas are most commonly diffuse large cell lymphomas and frequently manifest as an ill-defined, infiltrative mass. Atrial location is typical; the right atrium is most often affected. Pericardial thickening or effusion is often a common early feature of disease. Infiltration of atrial or ventricular walls with extension along epicardial surfaces is also a notable feature. At computed tomography, the attenuation of cardiac lymphoma may be similar to or lower than that of normal myocardium. At magnetic resonance imaging, it has variable signal intensity and contrast enhancement. Clinical manifestations may include pericardial effusion, cardiac arrhythmias, and a variety of nonspecific electrocardiographic abnormalities, notably first- to third-degree atrioventricular block. Treatment most commonly includes anthracycline-based chemotherapy and anti-CD20 treatment. Chemotherapy has been used alone or combined with radiation therapy. Palliative surgery has been performed, mainly for tumor debulking. The prognosis for patients with either primary or secondary lymphomatous heart involvement is usually poor; late diagnosis is one of the major factors affecting outcome.

Desmoid Tumor of the Rectus Abdominis Muscle in a Postpartum Patient

Desmoid Tumor of the Rectus Abdominis Muscle in a Postpartum Patient

144 Case report of severe reactivation of multiple sclerosis in a patient who had recently discontinued Natalizumab and who did not have progressive multifocal encephalopathy (PML)

BackgroundNatalizumab has been shown to be a cost-effective treatment for rapidly evolving severe relapsing–remitting multiple sclerosis (MS). However concern has arisen over the increased risk of PML with duration of...

Magnetic resonance imaging (MRI) and dynamic MRI evaluation of extranodal non-Hodgkin lymphoma in oral and maxillofacial regions

The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI), especially dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), in extranodal non-Hodgkin lymphoma (NHL) of oral and maxillofacial regions. Thirteen cases with extranodal NHL were examined using MRI. T1-weighted images (T1WI) and T2-weighted images (T2WI) or short TI inversion recovery (STIR) images were obtained in all cases. Contrast-enhanced images and DCE-MRI were acquired in 10 and 7 cases, respectively. On DCE-MRIs, we analyzed the parameters as follows: contrast index at maximal contrast enhancement (CImax), maximum contrast index (CI) gain/CImax ratio, and washout ratios (WR(300), WR(600), and WR(900)) at 300, 600, and 900 seconds after contrast medium injection. The signal intensity of all lesions was hypointense to isointense on T1WIs and showed variable contrast enhancement patterns. On T2WIs and STIR images, the signal intensity was isointense to hyperintense in almost all cases. Analysis of DCE-MRI parameters in extranodal NHLs resulted in the identification of 4 types of CI curves according to CImax and WR: (1) CImax greater than 2.0 and WR(900) greater than 40%, (2) CImax greater than 2.0 and WR(900) less than 40%, (3) CImax less than 1.5 and WR(900) greater than 40%, and (4) CImax less than 1.5 and WR(900) greater than 40%. The signal intensities on MRI were not specific to extranodal NHL and resembled those of other tumor types. When CImax was less than 1.5 or WR900 was less than 40%, these parameters contributed to diagnosis in extranodal NHLs.

Diffeomorphic Registration of Images with Variable Contrast Enhancement

Nonrigid image registration is widely used to estimate tissue deformations in highly deformable anatomies. Among the existing methods, nonparametric registration algorithms such as optical flow, or Demons, usually have the advantage of being fast and easy to use. Recently, a diffeomorphic version of the Demons algorithm was proposed. This provides the advantage of producing invertible displacement fields, which is a necessary condition for these to be physical. However, such methods are based on the matching of intensities and are not suitable for registering images with different contrast enhancement. In such cases, a registration method based on the local phase like the Morphons has to be used. In this paper, a diffeomorphic version of the Morphons registration method is proposed and compared to conventional Morphons, Demons, and diffeomorphic Demons. The method is validated in the context of radiotherapy for lung cancer patients on several 4D respiratory-correlated CT scans of the thorax with and without variable contrast enhancement.