Adjuvant radiotherapy after brain metastasectomy: analysis of consecutive cohort of 118 patients from real world practice.

Background: The aim of this retrospective study is to analyze a consecutive cohort of brain metastasis (BM) patients treated off clinical trials through combination of surgery and radiotherapy over the last 15 years in a tertiary neurooncology center. Materials and methods: All BM patients operated between 2007-2019 received adjuvant linac-based radiotherapy categorized to whole brain radiotherapy (WBRT) and tumor bed stereotactic radiotherapy. Survival outcomes and local control was analyzed. Results: In total, 118 patients were enrolled, those with stereotactic radiotherapy (41%) had better baseline characteristics mirrored in longer overall survival (OS) [18 vs. 7.1 months, p < 0.001; hazard ratio (HR) 0.47, p = 0.004] with median follow-up of 58 months. Cumulative incidence for local, distant, and extracranial control was not significantly different between groups, with 12-month cumulative control of 22% vs. 18%, 44% vs. 29%, and 35% vs. 32% for stereotactic and WBRT group, respectively. WBRT was an independent factor for better distal brain control. Conclusions: Real world data demonstrating significantly better overall survival in patients treated with postoperative targeted radiotherapy compared with postoperative WBRT is presented, with no significant difference in cumulative incidence for local or distant brain control. The majority of patients with targeted radiotherapy had a fractionated dose schedule with outcomes comparable to single-dose radiation trials of postoperative targeted radiotherapy.

The relationship between gadolinium enhancement and [18 F]fluorothymidine uptake in brain lesions with the use of hybrid PET/MRI.

BACKGROUND: To evaluate and compare the diagnostic power of [18F]FLT-PET with ceMRI in patients with brain tumours or other focal lesions. METHODS: 121 patients with suspected brain tumour or those after brain tumour surgery were enroled in this retrospective study (61 females, 60 males, mean age 37.3 years, range 1-80 years). All patients underwent [18F]FLT-PET/MRI with gadolinium contrast agent application. In 118 of these patients, a final diagnosis was made, verified by histopathology or by follow-up. Agreement between ceMRI and [18F]FLT-PET of the whole study group was established. Further, sensitivity and specificity of ceMRI and [18F]FLT-PET were calculated for differentiation of high-grade vs. low-grade tumours, high-grade vs. low-grade tumours together with non-tumour lesions and for differentiation of high-grade tumours from all other verified lesions. RESULTS: [18F]FLT-PET and ceMRI findings were concordant in 119 cases (98%). On closer analysis of a subset of 64 patients with verified gliomas, the sensitivity and specificity of both PET and ceMRI were identical (90% and 84%, respectively) for differentiating low-grade from high-grade tumours, if the contrast enhancement and [18F]FLT uptake were considered as hallmarks of high-grade tumour. For differentiation of high-grade tumours from low-grade tumours and lesions of nontumorous aetiology (e.g., inflammatory lesions or post-therapeutic changes) in a subgroup of 93 patients by visual evaluation, the sensitivity of both PET and ceMRI was 90%, whereas the specificity of PET was slightly higher (61%) compared to ceMRI (57%). By receiver operating characteristic analysis, the sensitivity and specificity were 82% and 74%, respectively, when the threshold of SUVmax in the tumour was set to 0.9 g/ml. CONCLUSION: We demonstrated a generally very high correlation of [18F]FLT accumulation with contrast enhancement visible on ceMRI and a comparable diagnostic yield in both modalities for differentiating high-grade tumours from low-grade tumours and lesions of other aetiology.

Significance of F-18 FDG PET/MRI in the search for the etiology of inflammation of unclear origin and fever of unknown origin.

PURPOSE: To evaluate the contribution of F-18 FDG-PET/MRI in the search for the etiology of the inflammation of unknown origin (IUO) and fever of unknown origin (FUO). MATERIAL AND METHODS: The study included 104 patients who underwent F-18 FDG-PET/MRI for IUO or FUO. The sensitivity, specificity, predictive values of the PET/MRI findings in relation to the final diagnosis of IUO/FUO were evaluated. A five-point Likert scale was used to semiquantitatively assess the probability of the cause of IUO/FUO based on PET/MRI finding. Furthermore, clinical (fever, arthralgia, weight loss, night sweats, age) and laboratory (C-reactive protein, leukocytes) parameters were monitored and compared with the true positivity rate of PET/MRI. RESULTS: In patients with definitively identified etiology of FUO and IUO, FDG-PET/MRI achieved a sensitivity of 96 %, specificity of 82 %, and positive and negative predictive values of 92 and 90 %. The cause of the IUO was determined in 71 patients (68.3 %). In 33 (31.7 %) patients, the etiology of IUO/FUO remained unknown, while in 25 (75.8 %) of them the symptoms resolved spontaneously and in 8 (24.2 %) patients they persisted without explanation even after 12 months of the follow-up. The most significant parameter in relation to subsequent PET/MRI finding was increased level of CRP, which was present in 96 % of true positive PET/MRI and normal CRP level was present in 56 % of true negative PET/MRI. CONCLUSION: Based on this study, FDG-PET/MRI is a suitable alternative for the investigation of IUO/FUO, this imaging technique has a very high sensitivity and negative predictive value.

Evaluating Magnetic Resonance Diffusion Properties Together with Brain Volumetry May Predict Progression to Multiple Sclerosis.

RATIONALE AND OBJECTIVES: Although the gold standard in predicting future progression from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) consists in the McDonald criteria, efforts are being made to employ various advanced MRI techniques for predicting clinical progression. This study's main aim was to evaluate the predictive power of diffusion tensor imaging (DTI) of the brain and brain volumetry to distinguish between patients having CIS with future progression to CDMS from those without progression during the following 2 years and to compare those parameters with conventional MRI evaluation. MATERIALS AND METHODS: All participants underwent an MRI scan of the brain. DTI and volumetric data were processed and various parameters were compared between the study groups. RESULTS: We found significant differences between the subgroups of patients differing by future progression to CDMS in most of those DTI and volumetric parameters measured. Fractional anisotropy of water diffusion proved to be the strongest predictor of clinical conversion among all parameters evaluated, demonstrating also higher specificity compared to evaluation of conventional MRI images according to McDonald criteria. CONCLUSION: Conclusion: Our results provide evidence that the evaluation of DTI parameters together with brain volumetry in patients with early-stage CIS may be useful in predicting conversion to CDMS within the following 2 years of the disease course.

Prospective Multiparametric Magnetic Resonance Monitoring of Changes in Lesions of Hyaline Cartilage of the Knee Joint After Treatment by Microfractures and Implantation of Biological Collagen Type I Matrix Implants .

RATIONALE AND OBJECTIVES: This study's aims were to depict changes in cartilage quality after surgical intervention using magnetic resonance (MR) examination and in content of glycosaminoglycans chains (GAGs) after two types of surgeries - chondral defect treatment by microfractures and scaffold implantation in combination with microfractures. MATERIALS AND METHODS: Twenty-five patients were studied: 14 with implants, 11 with microfractures. MR examination was made before surgery and 6, 12, and 18 months thereafter. Qualitative changes in cartilage were observed by means of delayed gadolinium enhanced magnetic resonance imaging of cartilage sequence using Gd-DTPA2- and Gd-DOTA. In each examination, GAGs content was determined at three locations: the defect, its surroundings, and a non-load-bearing reference area. RESULTS: Measured indices showed no statistically significant differences in changes within the defect area when comparing the two treatment types at individual time points of 6, 12, and 18 months. In the case of microfracture treatment, more substantial decrease in GAGs concentration occurred at month 6, whereas the greatest decline occurred at month 12 when using an implant. Change in GAGs content and decline in cartilage quality were substantial also in the reference area and close surroundings. CONCLUSIONS: Hyaline cartilage behaves as a unified whole, and change in GAGs content was marked also in locations with no morphological damage. Over the monitored period, no statistically significant difference between treatment types was noted as measured by GAGs content in the defect or its close surroundings. dGEMRIC is suitable for monitoring cartilage quality even if use of Gd-DTPA2- is not possible, because comparable results were achieved using Gd-DOTA.

MR Diffusion Properties of Cervical Spinal Cord as a Predictor of Progression to Multiple Sclerosis in Patients with Clinically Isolated Syndrome.

BACKGROUND AND PURPOSE: This study's aim was to investigate diffusion properties of the cervical spinal cord in patients with clinically isolated syndrome (CIS) through analysis of diffusion tensor imaging (DTI) data and thereby to assess the capacity of this technique for predicting the progression of CIS to clinically definite multiple sclerosis (CDMS). METHODS: The study groups were comprised of 47 patients with CIS (15 of them with progression to CDMS within 2 years of follow-up) and 57 asymptomatic controls. All patients and controls had undergone magnetic resonance imaging (MRI) of the cervical spine including DTI and brain MRI. Methodological approaches included histogram analysis of the cervical cord's diffusion parameters and evaluation of T2 hyperintense lesions of the spinal cord and brain. All parameters were compared between the study groups. Sensitivity and specificity calculations were then performed with a view to predicting conversion to CDMS. RESULTS: The patient subgroups defined by progression to CDMS differed significantly in values of fractional anisotropy (FA) kurtosis measured within white matter (WM) and normal-appearing WM (NAWM). The same parameters also differed significantly when patients with progression to CDMS were compared to healthy controls. Receiver operating characteristic (ROC) analysis revealed sensitivity and specificity of FA kurtosis of WM and NAWM of 93% and 72%, respectively, in terms of predicting CIS to CDMS progression. CONCLUSION: This study presents evidence that histogram analysis of diffusion parameters of the cervical spinal cord in patients with CIS may be helpful in predicting conversion to CDMS.

Voxelwise analysis of diffusion MRI of cervical spinal cord using tract-based spatial statistics.

Robust voxelwise analysis using tract-based spatial statistics (TBSS) together with permutation statistical method is standardly used in analyzing diffusion tensor imaging (DTI) of brain. A similar analytical method could be useful when studying DTI of cervical spinal cord. Based on anatomical data of sixty-four healthy volunteers, white (WM) and gray matter (GM) masks were created and subsequently registered into DTI space. Using TBSS, two skeleton types were created (single line and dilated for WM as well as GM). From anatomical data, percentage rates of overlap were calculated for all skeletons in relation to WM and GM masks. Voxelwise analysis of fractional anisotropy values depending on age and sex was conducted. Correlation of fraction anisotropy values with age of subjects was also evaluated. The two WM skeleton types showed a high overlap rate with WM masks (~94%); GM skeletons showed lower rates (56% and 42%, respectively, for single line and dilated). WM and GM areas where fraction anisotropy values differ between sexes were identified (p < .05). Furthermore, using voxelwise analysis such WM voxels were identified where fraction anisotropy values differ depending on age (p < .05) and in these voxels linear dependence of fraction anisotropy and age (r = -0.57, p < .001) was confirmed by regression analysis. This dependence was not proven when using WM anatomical masks (r = -0.21, p = .10). The analytical approach presented shown to be useful for group analysis of DTI data for cervical spinal cord.

In silico study of pseudoprogression in glioblastoma: collaboration of radiologists and radiation oncologists in the estimation of extent of high dose RT region.

BACKGROUND AND AIM: Oncologists play a vital role in the interpretation of radiographic results in glioblastoma patients. Molecular pathology and information on radiation treatment protocols among others are all important for accurate interpretation of radiology images. One important issue that may arise in interpreting such images is the phenomenon of tumor "pseudoprogression"; oncologists need to be able to distinguish this effect from true disease progression.Exact knowledge about the location of high-dose radiotherapy region is needed for valid determination of pseudoprogression according to RANO (Response Assessment in Neuro-Oncology) criteria in neurooncology. The aim of the present study was to evaluate the radiologists' understanding of a radiotherapy high-dose region in routine clinical practice since radiation oncologists do not always report 3-dimensional isodoses when ordering follow up imaging. METHODS: Eight glioblastoma patients who underwent postresection radiotherapy were included in this study. Four radiologists worked with their pre-radiotherapy planning MR, however, they were blinded to RT target volumes which were defined by radiation oncologists according to current guidelines. The aim was to draw target volume for high dose RT fields (that is the region, where they would consider that there may be a pseudoprogression in future MRI scans). Many different indices describing structure differences were analyzed in comparison with original per-protocol RT target volumes. RESULTS: The median volume for RT high dose field was 277 ccm (range 218 to 401 ccm) as defined per protocol by radiation oncologist and 87 ccm (range 32-338) as defined by radiologists (median difference of paired difference 31%, range 15-112%). The Median Dice index of similarity was 0.46 (range 0.14 - 0.78), the median Hausdorff distance 25 mm. CONCLUSION: Continuing effort to improve education on specific procedures in RT and in radiology as well as automatic tools for exporting RT targets is needed in order to increase specificity and sensitivity in response evaluation.

Structural and functional MRI correlates of T2 hyperintensities of brain white matter in young neurologically asymptomatic adults.

OBJECTIVES: Although white matter hyperintensities (WMHs) are quite commonly found incidentally, their aetiology, structural characteristics, and functional consequences are not entirely known. The purpose of this study was to quantify WMHs in a sample of young, neurologically asymptomatic adults and evaluate the structural and functional correlations of lesion load with changes in brain volume, diffusivity, and functional connectivity. METHODS: MRI brain scan using multimodal protocol was performed in 60 neurologically asymptomatic volunteers (21 men, 39 women, mean age 34.5 years). WMHs were manually segmented in 3D FLAIR images and counted automatically. The number and volume of WMHs were correlated with brain volume, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) data. Diffusion parameters measured within WMHs and normally appearing white matter (NAWM) were compared. RESULTS: At least 1 lesion was found in 40 (67%) subjects, median incidence was 1 lesion (interquartile range [IQR] = 4.5), and median volume was 86.82 (IQR = 227.23) mm3. Neither number nor volume of WMHs correlated significantly with total brain volume or volumes of white and grey matter. Mean diffusivity values within WMHs were significantly higher compared with those for NAWM, but none of the diffusion parameters of NAWM were significantly correlated with WMH load. Both the number and volume of WMHs were correlated with the changes of functional connectivity between several regions of the brain, mostly decreased connectivity of the cerebellum. CONCLUSIONS: WMHs are commonly found even in young, neurologically asymptomatic adults. Their presence is not associated with brain atrophy or global changes of diffusivity, but the increasing number and volume of these lesions correlate with changes of brain connectivity, and especially that of the cerebellum. KEY POINTS: • White matter hyperintensities (WMHs) are commonly found in young, neurologically asymptomatic adults. • The presence of WMHs is not associated with brain atrophy or global changes of white matter diffusivity. • The increasing number and volume of WMHs correlate with changes of brain connectivity, and especially with that of the cerebellum.

Contrast-enhanced ultrasonography.

Review summarizes state of the art of contrast-enhanced ultrasonography (CEUS), pinpoints technical basics and also economical comparison with other imaging methods. Most often indications of CEUS in different anatomical regions with differential diagnosis are discussed.

[Polymyalgia rheumatica]. / Polymyalgia rheumatica.

Polymyalgia rheumatica is the most frequent inflammatory disease of people over 50 years of age. It mainly affects the Caucasian race and roughly 2-3 times as many women. From the viewpoint of etiology, polymyalgia rheumatica is a complex disease. Involved in its origin is genetic predisposition, factors of age and outer environment. 16-21 % of patients with polymyalgia rheumatica may at the same time have symptoms of giant cell arteritis. Diagnosis is made primarily on the basis of clinical symptoms and it is supported by the presence of laboratory signs of inflammation. There is no specific diagnostic test available for diagnosing polymyalgia rheumatica. In recent time modern imaging devices, e.g. ultrasonography or positron emission tomography, can be used in diagnosing the disease. In the past a number of diagnostic and classification criteria were established which may be used in diagnosing of polymyalgia rheumatica in general practice. The differential diagnostics of the disease is extensive. Before the treatment commencement it is necessary to rule out the presence of another disease with manifestations simulating polymyalgia rheumatica. The treatment strategy should draw on the current EULAR/ACR Recommendations for the treatment of polymyalgia rheumatica issued in 2015.Key words: polymyalgia rheumatica - positron emission tomography - prognosis - treatment - ultrasonography.

18F-FDG PET/CT in polymyalgia rheumatica-a pictorial review.

Polymyalgia rheumatica (PMR) is one of the inflammatory rheumatic diseases that can potentially be detected by positron emission tomography/CT. High fluorine-18 fludeoxyglucose (18F-FDG) accumulation around the shoulders, sternoclavicular and hip joints are the most common pre-treatment features of patients with PMR. Another common sign is increased 18F-FDG uptake in extra-articular regions between columnal spinous processes, near ischial tuberosities and in the praepubic area. Some patients also present with high 18F-FDG uptake in main arteries, corresponding to the characteristics of giant cell arteritis. It is possible to observe a decrease or even a disappearance of 18F-FDG uptake after effective therapy, an event which may be useful for the monitoring of treatment as well as for detection of PMR relapse.

PET/CT imaging in polymyalgia rheumatica: praepubic 18F-FDG uptake correlates with pectineus and adductor longus muscles enthesitis and with tenosynovitis.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) is increasing in the diagnosis of polymyalgia rheumatica (PMR), one of the most common inflammatory rheumatic diseases. In addition to other locations, increased 18F-FDG accumulation has been detected in the praepubic region in some patients. However, a deeper description and pathophysiological explanation of this increased praepubic accumulation has been lacking. The aim of the presented study is to confirm a decrease in praepubic 18F-FDG accumulation in response to therapy and to describe potential correlations to other 18F-FDG PET/CT scan characteristics during the course of disease. As a secondary objective, we describe the pathological aspects of the observed praepubic 18F-FDG uptake. PATIENTS AND METHODS: A retrospective review of patients with newly suspected PMR undergoing baseline and follow up 18F-FDG PET/CT between February 2010 and March 2016 is given. Those with a visually detected presence of praepubic 18F-FDG accumulation were further analysed. The uptake was assessed visually and also semi-quantitatively in the defined region of interest by calculation of target-to-liver ratios. Other regions typical for PMR were systematically described as well (shoulders, hips, sternoclavicular joints, ischiogluteal bursae, spinous interspaces). RESULTS: Twenty-three out of 89 screened patients (26%) presented with initial praepubic 18F-FDG PET/CT positivity, 15 of whom also underwent follow up 18F-FDG PET/CT examination. Five out of 15 patients presented with increased 18F-FDG accumulation in large arteries as a sign of giant cell arteritis. During follow up examination, decrease in 18F-FDG accumulation caused by therapeutic intervention was observed in all evaluated locations in all analysed patients and no new positivity was indicated, including periarticular, extraarticular tissues or target large vessels. Praepubical accumulation of 18F-FDG was diminished in all patients (15/15, 100%) after treatment with steroids. CONCLUSIONS: Increased praepubic 18F-FDG uptake in patients with PMR is relatively common and this region should be systematically evaluated during differential diagnosis of rheumatic and malignant disease. Praepubic inflammation is probably related to enthesitis and tenosynovitis at the origin of pectineus and adductor longus muscles ventrally from the pubis.

Spinal Cord MR Diffusion Properties in Patients with Degenerative Cervical Cord Compression.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has previously been used as a biomarker of myelopathy in patients with degenerative cervical cord compression (DCCC). However, many factors may affect the diffusion properties of the spinal cord. This prospective study seeks to identify sources of variability in spinal cord DTI parameters in both DCCC patients and healthy subjects. METHODS: The study group included 130 patients with DCCC confirmed by magnetic resonance imaging and 71 control subjects without signs of DCCC. DTI data of the cervical spine were acquired in all subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured at different levels of the spinal cord (SCLs). Statistical data analysis was then used to determine diffusion parameters in terms of age, sex, SCL, and spinal cord compression. RESULTS: Significant variations in FA and ADC values emerged when several spinal cord levels were mutually compared in the control group. FA values correlated significantly with age in the DCCC group and sex had a significant influence on ADC values in both groups. The two diffusion parameters in the DCCC group differed significantly between patients with clinical signs of mild-to-moderate myelopathy compared with asymptomatic patients, and correlated with measurements of spinal canal morphology. CONCLUSIONS: Diffusion parameters of the cervical spinal cord were thus shown to respond significantly to spinal cord compression, but were subject to interaction with several other factors including sex, age, and SCL. These findings may be important to the interpretation of DTI measurements in individual patients.

Diffusion Tensor Imaging in Radiation-Induced Myelopathy.

Radiation myelopathy (RM) is a rare complication of spinal cord irradiation. Diagnosis is based on the history of radiotherapy, laboratory tests, and magnetic resonance imaging of the spinal cord. The MRI findings may nevertheless be quite unspecific. In this paper, we describe the findings of diffusion tensor imaging in a case of the delayed form of RM. We observed areas of restricted diffusion within the spinal cord which probably corresponded to the ischemic changes. This would concur with the currently accepted pathogenetic theory concerning RM.

Magnetic resonance diffusion tensor imaging in patients with cervical spondylotic spinal cord compression: correlations between clinical and electrophysiological findings.

STUDY DESIGN: A prospective study evaluating a cohort of patients with spondylotic cervical spine compression. OBJECTIVE: To analyze the potential of diffusion tensor imaging (DTI) of the cervical spinal cord in the detection of changes associated with spondylotic myelopathy, with particular reference to clinical and electrophysiological findings. SUMMARY OF BACKGROUND DATA: Conventional magnetic resonance imaging (MRI) may provide confusing findings because of a frequent disproportion between the degree of the spinal cord compression and clinical symptoms. The DTI is known to be more sensitive to subtle pathological changes of the spinal cord compared with conventional MRI. METHODS: The DTI of the cervical spinal cord was performed within a group of 52 patients with spondylotic spinal cord compression and 13 healthy volunteers on a 1.5-T MRI scanner. All patients underwent clinical examination that differentiated between asymptomatic and symptomatic myelopathy subgroups, and 45 patients underwent electrophysiological examination. We measured the apparent diffusion coefficient and fractional anisotropy of the spinal cord at C2/C3 level without compression and at the maximal compression level (MCL). Sagittal spinal canal diameter, cross-sectional spinal cord area, and presence of T2 hyperintensity at the MCL were also recorded. Nonparametric statistical testing was used for comparison of controls with subgroups of patients. RESULTS: Significant differences in both the DTI parameters measured at the MCL, between patients with compression and control group, were found, while no difference was observed at the noncompression level. Moreover, fractional anisotropy values were lower and apparent diffusion coefficient values were higher at the MCL in the symptomatic patients than in the asymptomatic patients. The DTI showed higher potential to discriminate between clinical subgroups in comparison with standard MRI parameters and electrophysiological findings. CONCLUSION: The DTI appears to be a promising imaging modality in patients with spondylotic spinal cord compression. It reflects the presence of symptomatic myelopathy and shows considerable potential for discriminating between symptomatic and asymptomatic patients.