Prevalence of TERT Promoter Mutations in Orbital Solitary Fibrous Tumors.

The orbital manifestation of a solitary fibrous tumor (SFT) is exceptionally rare and poses specific challenges in diagnosis and treatment. Its rather exceptional behavior among all SFTs comprises a high tendency towards local recurrence, but it rarely culminates in metastatic disease. This raises the question of prognostic factors in orbital SFTs (oSFTs). Telomerase reverse transcriptase (TERT)-promoter mutations have previously been linked to an unfavorable prognosis in SFTs of other locations. We analyzed the prevalence of TERT promoter mutations of SFTs in the orbital compartment. We performed a retrospective, descriptive clinico-histopathological analysis of nine cases of oSFTs between the years of 2017 and 2021. A TERT promoter mutation was present in one case, which was classified with intermediate metastatic risk. Local recurrence or progress occurred in six cases after primary resection; no distant metastases were reported. Multimodal imaging repeatedly showed particular morphologic patterns, including tubular vascular structures and ADC reduction. The prevalence of the TERT promoter mutation in oSFT was 11%, which is similar to the prevalence of extra-meningeal SFTs of the head and neck and lower than that in other extra-meningeal compartments. In the present study, the TERT promoter mutation in oSFT manifested in a case with an unfavorable prognosis, comprising aggressive local tumor growth, local recurrence, and eye loss.

Ophthalmic Magnetic Resonance Imaging: Where Are We (Heading To)?

Magnetic resonance imaging of the eye and orbit (MReye) is a cross-domain research field, combining (bio)physics, (bio)engineering, physiology, data sciences and ophthalmology. A growing number of reports document technical innovations of MReye and promote their application in preclinical research and clinical science. Realizing the progress and promises, this review outlines current trends in MReye. Examples of MReye strategies and their clinical relevance are demonstrated. Frontier applications in ocular oncology, refractive surgery, ocular muscle disorders and orbital inflammation are presented and their implications for explorations into ophthalmic diseases are provided. Substantial progress in anatomically detailed, high-spatial resolution MReye of the eye, orbit and optic nerve is demonstrated. Recent developments in MReye of ocular tumors are explored, and its value for personalized eye models derived from machine learning in the treatment planning of uveal melanoma and evaluation of retinoblastoma is highlighted. The potential of MReye for monitoring drug distribution and for improving treatment management and the assessment of individual responses is discussed. To open a window into the eye and into (patho)physiological processes that in the past have been largely inaccessible, advances in MReye at ultrahigh magnetic field strengths are discussed. A concluding section ventures a glance beyond the horizon and explores future directions of MReye across multiple scales, including in vivo electrolyte mapping of sodium and other nuclei. This review underscores the need for the (bio)medical imaging and ophthalmic communities to expand efforts to find solutions to the remaining unsolved problems and technical obstacles of MReye, with the objective to transfer methodological advancements driven by MR physics into genuine clinical value.

Author Correction: Evaluation of T1 relaxation time in prostate cancer and benign prostate tissue using a Modified Look-Locker inversion recovery sequence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluation of T1 relaxation time in prostate cancer and benign prostate tissue using a Modified Look-Locker inversion recovery sequence.

Purpose of this study was to evaluate the diagnostic performance of T1 relaxation time (T1) for differentiating prostate cancer (PCa) from benign tissue as well as high- from low-grade PCa. Twenty-three patients with suspicion for PCa were included in this prospective study. 3 T MRI including a Modified Look-Locker inversion recovery sequence was acquired. Subsequent targeted and systematic prostate biopsy served as a reference standard. T1 and apparent diffusion coefficient (ADC) value in PCa and reference regions without malignancy as well as high- and low-grade PCa were compared using the Mann-Whitney U test. The performance of T1, ADC value, and a combination of both to differentiate PCa and reference regions was assessed by receiver operating characteristic (ROC) analysis. T1 and ADC value were lower in PCa compared to reference regions in the peripheral and transition zone (p < 0.001). ROC analysis revealed high AUCs for T1 (0.92; 95%-CI, 0.87-0.98) and ADC value (0.97; 95%-CI, 0.94 to 1.0) when differentiating PCa and reference regions. A combination of T1 and ADC value yielded an even higher AUC. The difference was statistically significant comparing it to the AUC for ADC value alone (p = 0.02). No significant differences were found between high- and low-grade PCa for T1 (p = 0.31) and ADC value (p = 0.8). T1 relaxation time differs significantly between PCa and benign prostate tissue with lower T1 in PCa. It could represent an imaging biomarker for PCa.

[Magnetic Resonance Imaging of the Orbital Cavity: Indications and Diagnostic Possibilities]. / MRT-Bildgebung der Orbita: Indikationsspektrum und diagnostische Möglichkeiten.

Today, magnetic resonance imaging (MRI) is considered the diagnostic tool of choice for eye and orbital pathologies. In this article, the MR image characteristics of relevant pathologies are illustrated with case-based examples in the context of clinical findings. Vascular pathologies (such as capillary and cavernous hemangioma), inflammatory diseases (such as endocrine orbitopathy), and neoplasms (such as lymphoma, uveal melanoma, retinoblastoma, and ocular/orbital metastasis) are described. Additionally, the role of MRI in the acute clinical setting and in trauma are discussed. Technical aspects of MRI encompassing field strength and the utilization of receiver coils to optimize image quality and achieve high spatial resolution are explained. Next to the use of common sequences (T1- and T2-weighted sequences) used in standard anatomic imaging (sAI), the article demonstrates the potential of "multiparametric imaging" (diffusion-weighted imaging, DWI, and dynamic contrast-enhanced imaging, DCE). These innovative MRI sequences depict functional tissue features in addition to pure morphology and thus facilitate radiological assessment.

DCE-MR imaging of orbital lesions: diagnostic performance of the tumor flow residence time τ calculated by a multi-compartmental pharmacokinetic tumor model based on individual factors.

BACKGROUND: Differentiating benign from malignant orbital lesions by imaging and clinical presentation can be challenging. PURPOSE: To differentiate benign from malignant orbital masses using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on tumor flow residence time τ calculated with the aid of a pharmacokinetic tumor model. MATERIAL AND METHODS: Sixty patients with orbital masses were investigated by 3-T MRI including dynamic sequences. The signal intensity-time curve after i.v. contrast medium administration within lesions was approximated by Gd-concentration profiles on the basis of model calculations where the tumor is embedded in a whole-body kinetic model. One output of the model was tumor flow residence time τ, defined as the ratio of the tumor volume and the tumor blood flow rate. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of τ. The results were compared with those of Ktrans, kep, ve, iAUC, and ADC. RESULTS: Thirty-one benign and 29 malignant orbital masses were identified (reference standard: histopathology, clinical characteristics). Mean τ was significantly longer for benign masses (94 ± 48 s) than for malignant masses (21 ± 19 s, P < 0.001). ROC analysis revealed the highest area under the curve (AUC = 0.94) for τ in orbital masses compared to standard methods. CONCLUSION: Tumor flow residence times τ of benign and malignant orbital masses are valuable in the diagnostic work-up of orbital tumors. Measures of diagnostic accuracy were superior for τ compared to ADC, Ktrans, ve, and iAUC.

Proton Beam Irradiation: A Safe Procedure in Postequatorial Extraocular Extension From Uveal Melanoma.

PURPOSE: This study was performed to show long-term outcomes concerning metastasis rates and local recurrence rates after primary proton beam therapy in uveal melanoma with posterior extraocular extension (EOE) with the main focus on optic nerve invasion. DESIGN: Retrospective case series. METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma with posterior EOE between July 1998 and August 2010 were included. EOE was detected either upon sonography at primary examination or during the surgical application of tantalum clips onto the sclera. Ultrasound was performed in each patient before surgery, and if EOE was detected, a magnetic resonance imaging (MRI) scan was performed to confirm EOE. All patients with tumors exceeding 6 mm in thickness or abutting the optic disc received a 1.5 Tesla MRI scan after clip surgery. To assess EOE during follow-up, either ultrasound examinations or-if initially detected only by MRI-MRI scans were performed during follow-up. RESULTS: A total of 27 patients underwent primary proton beam therapy. The EOE was separated into 3 growth types: optic nerve infiltration in 10 patients, vortex vein infiltration in 9 patients, and transscleral growth postequatorially in 8 patients. No local recurrences were found during the overall median follow-up of 80 months (11-168 months). Metastasis rates correlated with AJCC stages but not EOE volume. CONCLUSION: This study shows that posterior EOE can safely be treated by proton beam therapy, even if the optic nerve is infiltrated. MRI enables safe detection of optic nerve invasion.

Characterization of orbital masses by multiparametric MRI.

OBJECTIVES: DWI and dynamic contrast enhanced (DCE) MR imaging are techniques that allow insight to tumor vascularity and cellularity. We evaluated the diagnostic performance of multiparametric MRI (mp-MRI) in distinguishing benign from malignant orbital masses using standard anatomic imaging (sAI), DWI and DCE. MATERIALS AND METHODS: This prospective IRB approved study with written informed consent included 65 patients. mp-MRI at 3 Tesla including DWI and DCE was performed in all patients. Parametric maps were generated for obtaining the perfusion parameters including K(trans), kep, ve and iAUC and time-signal intensity curves were recorded to determine the curve pattern. Two radiologists rated the likelihood of malignancy on a five-point scale in three separate, randomized reading sessions (initially only sAI, afterwards sAI+either DWI or DCE and finally sAI+DWI+DCE). Data was statistically analyzed. RESULTS: 33 Patients had malignant orbital masses and 32 patients had benign orbital masses (reference standard histopathology in 35 cases and clinical follow-up in 30 patients). The mean ADC of malignant masses differed significantly from the mean (SD) ADC of benign masses (0.825 [0.437]×10(-3)mm(2)/s and 1.257 [0.576]×10(-3)mm(2)/s, respectively) (p=0.001). K(trans), kep and iAUC were significantly higher in malignant masses (p<0.01). The reading of sAI only resulted in a moderate specificity but poor sensitivity in differentiating benign from malignant lesions. Adding DWI and DCE images improved specificity and sensitivity considerably, being the highest for the combined reading of all sequences. CONCLUSION: mp-MRI is a helpful tool in differentiating malignant orbital lesions from benign masses and should therefore be included in the routine diagnostic protocol for orbital imaging.

Equilibrium-phase MR angiography: Comparison of unspecific extracellular and protein-binding gadolinium-based contrast media with respect to image quality.

The purpose of this study was to compare contrast and image quality of whole-body equilibrium-phase high-spatial-resolution MR angiography using a non-protein-binding unspecific extracellular gadolinium-based contrast medium with that of two contrast media with different protein-binding properties. 45 patients were examined using either 15 mL of gadobutrol (non-protein-binding, n = 15), 32 mL of gadobenate dimeglumine (weakly protein binding, n = 15) or 11 mL gadofosveset trisodium (protein binding, n = 15) followed by equilibrium-phase high-spatial-resolution MR-angiography of four consecutive anatomic regions. The time elapsed between the contrast injection and the beginning of the equilibrium-phase image acquisition in the respective region was measured and was up to 21 min. Signal intensity was measured in two vessels per region and in muscle tissue. Relative contrast (RC) values were calculated. Vessel contrast, artifacts and image quality were rated by two radiologists in consensus on a five-point scale. Compared with gadobutrol, gadofosveset trisodium revealed significantly higher RC values only when acquired later than 15 min after bolus injection. Otherwise, no significant differences between the three contrast media were found regarding vascular contrast and image quality. Equilibrium-phase high-spatial-resolution MR-angiography using a weakly protein-binding or even non-protein-binding contrast medium is equivalent to using a stronger protein-binding contrast medium when image acquisition is within the first 15 min after contrast injection, and allows depiction of the vasculature with high contrast and image quality. The protein-binding contrast medium was superior for imaging only later than 15 min after contrast medium injection.

Magnetic resonance imaging based morphologic evaluation of the pineal gland for suspected pineoblastoma in retinoblastoma patients and age-matched controls.

PURPOSE: The purpose of this study was to evaluate the morphologic magnetic resonance imaging (MRI) characteristics of the pineal gland in retinoblastoma (Rb) patients without and with pineoblastoma in comparison to age-matched controls to improve early identification of pineoblastomas (trilateral retinoblastoma, TRb). METHODS AND MATERIALS: 80 patients with retinoblastoma and 80 age-matched controls who had undergone brain MRI were included in this retrospective institutional review board approved cohort study. Two readers analyzed the following MR characteristics of the pineal gland: signal intensity on T1- and T2-weighted images, enhancement pattern, delineation of the gland, presence of cystic component, size of pineal gland and size of pineal cysts, respectively. A third reader assessed all images for the presence or absence of pineoblastoma. RESULTS: 3 patients were positive (TRb cohort) and 77 negative for pineoblastoma (non-TRb cohort). The mean maximum diameter of the pineal gland was 6.4mm in Rb patients and 6.3mm in age-matched controls. The mean volume of the pineal gland in Rb patients was 93.1mm(3) and was 87.6mm(3) in age-matched controls. Considering all available MRI scans the mean maximum diameter of the pineal gland in TRb patients was 11.2mm and the mean volume in TRb patients was 453.3mm(3). The third reader identified pineoblastomas with a sensitivity of 100% (3 of 3) and a specificity of 94% (72 of 77). CONCLUSION: Our non-TRb patients did not show significant differences in the size of the pineal gland and pineal gland cysts compared to age-matched controls. The presented data can serve as a reference for the volume of normal pineal glands and pineal cysts in the diagnostic work-up of Rb patients with suspected pineoblastoma.

Predicting Lens Diameter: Ocular Biometry With High-Resolution MRI.

PURPOSE: The aim of this study was to correlate different biometric dimensions of the eye as measured from ocular magnetic resonance imaging (MRI) scans to predict the lens diameter. METHODS: High-resolution ocular MRI scans of 100 eyes of 100 patients were reviewed. Various anatomical variables of the eye such as the axial length, the globe diameter, and the lens dimensions were measured. Also, the distances between the ciliary sulcus and angle-to-angle were measured. A partial least square (PLS) regression model was built to analyze which variables influence the model regarding the lens dimensions. RESULTS: Sixty-two eyes of 62 patients were included in the final analysis. The lens diameter ratio (horizontal to vertical) was 0.93 (SD: 0.04; 0.83-1.00). The partial least square regression showed a significant connection (P < 0.001) between the horizontal and vertical diameter. The partial least square regression model that included the globe diameter and the axis length resulted in the best prediction for the horizontal lens diameter. Similar to the horizontal lens diameter, globe diameter was the best predictor for the vertical lens diameter followed by the distance of the ciliary sulcus. White-to-white distance, distance of the ciliary sulcus, and axial eye length were found to have a high influence on the angle-to-angle distance. CONCLUSIONS: The introduced models may serve as tools to predict the capsular bag biometry in a preoperative setting for cataract surgery or lens refilling procedures.

Dynamic contrast-enhanced MRI of ocular melanoma.

Dynamic contrast-enhanced MRI is used for the assessment of microvasculature in several tumours. We aimed to assess the contrast signal enhancement characteristics of ocular melanoma. Forty patients with ocular melanoma were prospectively investigated with ocular MRI including dynamic contrast-enhanced sequences over a 13-month period. A region-of-interest analysis of the images was carried out to calculate signal enhancement characteristics after a contrast injection. Clinical follow-up data such as extraocular spread and development of liver metastasis were compared with the signal enhancement characteristics of the ocular melanoma. In 39 patients (98%), the ocular melanomas showed an early strong signal enhancement after contrast injection, resulting in a mean time of maximum enhancement of 49 s. Clinical follow-up was available in 28 patients (70%) and indicated that the peak signal intensity was significantly increased (P=0.039) in patients who developed extraocular spread or liver metastasis at a later stage. Ocular melanoma shows signal enhancement characteristics of hypervascular neoplasms. This study provides baseline curve pattern data that may be useful for assessing changes in vascularity, for example during therapy response. Furthermore, the study showed that a strong signal enhancement of the ocular melanoma might be linked to a less favourable prognosis.

Tract-based spatial statistics of the olfactory brain in patients with multiple sclerosis.

PURPOSE: To investigate diffusion tensor abnormalities, e.g. fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD), in olfactory structures of multiple sclerosis (MS) patients using diffusion tensor imaging (DTI). METHODS: Institutional review board-approved prospective study on 30 MS patients and 12 healthy controls investigated with MRI including DTI. Central olfactory structures were labelled on each patient's and healthy contro''s DTI volume. The diffusion tensor was determined in the central olfactory structures in MS patients. Tract-based spatial statistics (TBSS) was used to quantify the streamlines outgoing from the olfactory structures and to quantify changes in FA, MD, and RD within olfactory structures. These brain changes were correlated with olfactory function measured as TDI (Threshold, Discrimination, Identification) scores in patients and compared to our own reference group of 30 healthy volunteers. RESULTS: Central olfactory structures in the MNI (Montreal Neurological Institute) data volume comprise 4808 voxels (4808 mm(3)). TFCE (Threshold-free cluster enhancement) and cluster analysis of patients identified a total of 127 voxels in one cluster with a significantly decreased FA (p<0.05) and none for MD and RD within olfactory structures compared to healthy controls. The correlation with the age-normalised Identification subscore of the TDI score increased the significant number of voxels with decreased FA to 208 voxels, with increased MD to 370 and with increased RD 364 voxels at the same region. CONCLUSION: The decrease in FA and increase of MD and RD correlate with the degree of identification impairment of olfactory function in MS patients and clusters of abnormalities were identified on a MNI data volume.

Ocular MR imaging: evaluation of different coil setups in a phantom study.

PURPOSE: Small loop surface coils are generally recommended for ocular magnetic resonance (MR) imaging, but the optimal coil setup has not been systematically investigated. In this phantom study, we investigated which coil setup of those coils available for our MR imaging system provides the highest signal-to-noise ratio (SNR) in ocular MR imaging at 1.5 tesla. MATERIALS AND METHODS: Using a phantom to simulate the eyeball and the orbital fat, we employed loop surface coils of 4- and 6-cm diameter and a multi-channel head coil to obtain images using a T1-weighted spin-echo sequence and then measured the SNR for each coil and coil combination. RESULTS: Use of the 6-cm loop coil alone yielded the highest mean SNR (27.5). Even in superficial regions (mesial and temporal), the SNR was higher using the 6-cm loop coil (33.6 and 45.5) than the 4-cm loop coil (28.0 and 33.8). Additional use of the head coil reduced the mean SNR to 10.4. CONCLUSION: This quantitative analysis suggests that use of a 6-cm loop surface coil offers the best results in ocular MR imaging. Combinations of loop coils or additional use of a head coil cannot be recommended because higher noise degrades image quality.

Diffusion-weighted imaging of ocular melanoma.

OBJECTIVES: Diffusion-weighted imaging (DWI) allows characterization of masses on the basis of their cellular density. We hypothesized that ocular melanoma has a marked diffusion restriction as seen in other malignant tumors. Furthermore, we aimed to assess whether DWI is useful to differentiate ocular melanoma from retinal detachment. MATERIALS AND METHODS: The institutional review board approved the prospective study on 44 patients investigated with ocular magnetic resonance imaging including DWI during a 9-month period. A region-of-interest analysis of diffusion-weighted images with b values of 0 and 1000 s/mm was performed to calculate the apparent diffusion coefficient (ADC) of the ocular melanoma and the retinal detachment. Three patients were excluded because DWI was nondiagnostic owing to severe artifacts; in 1 patient, the melanoma was too small for ADC calculation. Therefore, 40 patients were included in the final analysis. Ocular melanomas and detachments were compared with respect to their ADC values. The image quality of DWI was qualitatively scored by 2 readers in consensus on a 3-point scale from 1 (minor artifacts) to 3 (major artifacts). RESULTS: Ocular melanomas showed a marked diffusion restriction, and the mean (SD) ADC was 891 (172) × 10 mm/s. Twenty-nine patients (66%) had retinal detachment. The mean ADC of the ocular melanoma differed significantly (P < 0.001) from the mean ADC of the retinal detachment (1986 [375] × 10 mm/s). The image quality of DWI was rated 1 in 38 patients, 2 in 3 patients, and 3 in 3 patients. CONCLUSIONS: Ocular melanoma shows a marked diffusion restriction with an ADC of less than 1000 mm/s, which is in concordance with other malignant tumor entities. Diffusion-weighted imaging helps differentiating ocular tumors from retinal detachment and should therefore be included in the ocular magnetic resonance imaging protocol if an ocular mass is suspected.