Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors.

OBJECTIVE: To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. METHODS: In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. RESULTS: CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. CONCLUSIONS: The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

Multi-center reproducibility of structural, diffusion tensor, and resting state functional magnetic resonance imaging measures.

PURPOSE: The aim of this study is to assess multi-center reproducibility and longitudinal consistency of MRI imaging measurements, as part of a phase III longitudinal multi-center study comparing the neurotoxic effect following prophylactic cranial irradiation with hippocampal avoidance (HA-PCI), in comparison with conventional PCI in patients with small-cell lung cancer. METHODS: Harmonized MRI acquisition protocols from six participating sites and two different vendors were compared using both physical and human phantoms. We assessed variability across sites and time points by evaluating various phantoms and data including hippocampal volume, diffusion metrics, and resting-state fMRI, from two healthy volunteers. RESULTS: We report average coefficients of variation (CV) below 5% for intrascanner, intravendor, and intervendor reproducibility for both structural and diffusion imaging metrics, except for diffusion metrics obtained from tractography with average CVs ranging up to 7.8%. Additionally, resting-state fMRI showed stable temporal SNR and reliable generation of subjects DMN across vendors and time points. CONCLUSION: These findings indicate that the presented multi-site MRI acquisition protocol can be used in a longitudinal study design and that pooling of the acquired data as part of the phase III longitudinal HA-PCI project is possible with careful monitoring of the results of the half-yearly QA assessment to follow-up on potential scanner-related longitudinal changes in image quality.

Cyclic movement frequency is associated with muscle typology in athletes.

There is a continuing research interest in the muscle fiber type composition (MFTC) of athletes. Recently, muscle carnosine quantification by proton magnetic resonance spectroscopy (1 H-MRS) was developed as a new non-invasive method to estimate MFTC. This cross-sectional study aims to better understand estimated MFTC in relation to (a) different disciplines within one sport; (b) cyclic sport exercise characteristics; (c) within-athlete variability; and (d) athlete level. A total of 111 elite athletes (74 runners, 7 triathletes, 11 swimmers, 14 cyclists and 5 kayakers) and 188 controls were recruited to measure muscle carnosine in gastrocnemius and deltoid muscle by 1 H-MRS. Within sport disciplines, athletes were divided into subgroups (sprint-, intermediate-, and endurance-type). The controls were used as reference population to allow expression of the athletes' data as Z-scores. Within different sports, endurance-type athletes systematically showed the lowest Z-score compared to sprint-type athletes, with intermediate-type athletes always situated in between. Across the different sports disciplines, carnosine content showed the strongest significant correlation with cyclic movement frequency (R = 0.86, P = 0.001). Both within and between different cyclic sports, estimated MFTC was divergent between sprint- and endurance-type athletes. Cyclic movement frequency, rather than exercise duration came out as the most determining factor for the optimal estimated MFTC in elite athletes.

A neuroradiologist's guide to arterial spin labeling MRI in clinical practice.

Arterial spin labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF). This review provides a practical guide and overview of the clinical applications of ASL of the brain, as well its potential pitfalls. The technical and physiological background is also addressed. At present, main areas of interest are cerebrovascular disease, dementia and neuro-oncology. In cerebrovascular disease, ASL is of particular interest owing to its quantitative nature and its capability to determine cerebral arterial territories. In acute stroke, the source of the collateral blood supply in the penumbra may be visualised. In chronic cerebrovascular disease, the extent and severity of compromised cerebral perfusion can be visualised, which may be used to guide therapeutic or preventative intervention. ASL has potential for the detection and follow-up of arteriovenous malformations. In the workup of dementia patients, ASL is proposed as a diagnostic alternative to PET. It can easily be added to the routinely performed structural MRI examination. In patients with established Alzheimer's disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns seen with PET. Studies on ASL in brain tumour imaging indicate a high correlation between areas of increased CBF as measured with ASL and increased cerebral blood volume as measured with dynamic susceptibility contrast-enhanced perfusion imaging. Major advantages of ASL for brain tumour imaging are the fact that CBF measurements are not influenced by breakdown of the blood-brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies.

MRI analysis of muscle/fat index of the superficial and deep neck muscles in an asymptomatic cohort.

All muscles of the neck have a role in motion and postural control of the cervical region. The aim of this study was to investigate the difference in muscle/fat index between (1) cervical flexors and extensors and (2) deep and superficial neck muscles. Twenty-six healthy subjects participated in the study. Magnetic resonance imaging (MRI) was used to quantify muscle fat indices in different cervical flexor and extensor muscles at the C4-C5 level. Overall, the ventral muscles had a significantly lower fat content compared with the dorsal muscles (P < or = 0.001). For the cervical extensors, significant differences between the muscle/fat index of the deep and superficial muscles were found (P < or = 0.001). For the cervical flexors, there were no significant differences between the different muscles. The higher fat content in the dorsal muscles can be explained by a discrepancy in function between the spine extensors and flexors, reflected in a different muscle fiber distribution. The rather small differences between superficial and deep neck muscles are in line with recent findings that have demonstrated that both muscles groups exhibit phasic activity during isometric muscles contractions and the presumption that there is no difference in fiber type distribution between superficial and deep neck muscles.

Comparison of unsupervised classification methods for brain tumor segmentation using multi-parametric MRI.

Tumor segmentation is a particularly challenging task in high-grade gliomas (HGGs), as they are among the most heterogeneous tumors in oncology. An accurate delineation of the lesion and its main subcomponents contributes to optimal treatment planning, prognosis and follow-up. Conventional MRI (cMRI) is the imaging modality of choice for manual segmentation, and is also considered in the vast majority of automated segmentation studies. Advanced MRI modalities such as perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) have already shown their added value in tumor tissue characterization, hence there have been recent suggestions of combining different MRI modalities into a multi-parametric MRI (MP-MRI) approach for brain tumor segmentation. In this paper, we compare the performance of several unsupervised classification methods for HGG segmentation based on MP-MRI data including cMRI, DWI, MRSI and PWI. Two independent MP-MRI datasets with a different acquisition protocol were available from different hospitals. We demonstrate that a hierarchical non-negative matrix factorization variant which was previously introduced for MP-MRI tumor segmentation gives the best performance in terms of mean Dice-scores for the pathologic tissue classes on both datasets.

Comparison between 1 T MRI and non-MRI based volumetry in inoculated tumours in mice.

Tumour volume is an important therapeutic endpoint for mouse tumour models in the evaluation of new chemotherapeutic drugs and in pre-clinical evaluation of new radioimmunotherapy pharmaceuticals. In this study, two 1 T MRI-based methods both using T1-T2 hybrid weighting, a manual method (determination of the area per slice) and a semi-automated method (using thresholding), are compared with two classical methods, the abovementioned calliper method and volumetry by water displacement after dissection of the tumour. Interoperator and intraoperator differences for both MRI-based methods were good (no differences p<0.05 using a repeated measures analysis of variance (ANOVA) test). Correlation between the different methods was excellent. No significant differences were obtained (p<0.05), except for the semi-automated method, because it automatically excludes necrotic regions from the tumour. Therefore, we conclude that both manual and semi-automated tumour volumetry in subcutaneous tumour bearing athymic mice by low-field MRI are accurate and reliable methods. The semi-automated method is especially useful for larger tumour volumes, since it accounts for necrotic areas within the tumour.

Three-dimensional dosimetry using polymer gel and magnetic resonance imaging applied to the verification of conformal radiation therapy in head-and-neck cancer.

BACKGROUND AND PURPOSE: It was our aim to investigate NMR-based BANG gel dosimetry as a three-dimensional dosimetry technique in conformal radiotherapy. MATERIALS AND METHODS: The BANG gel consisting of gelatin, water and co-monomers was first validated in a cylindrical glass flask for a single standard beam. Next, the gel contained in a human neck-shaped cast was used to verify a treatment plan for the conformal irradiation of a concave tumour in the lower neck. Magnetic resonance relaxation rate images were acquired and, based on an appropriate calibration of the gel, converted to absorbed dose distributions. The resulting maps were compared with dose distributions measured using radiographic film. RESULTS: The gel-measured dose profiles of standard beams agreed within 3% (root mean square difference) with the profiles measured with high spatial resolution by a diamond detector. For the multi-beam conformal treatment, the difference map between gel-measured and film-measured dose distributions revealed a noise component and a more systematic deviation including structural or space-coherent patterns. The mean absolute value of the difference amounted to 8%. A number of possible causes for this deviation are designated. CONCLUSIONS: Polymer gel dosimetry in combination with magnetic resonance imaging is a promising method for dosimetric verification of conformal radiotherapy.

Human brain chemical shift imaging at age 60 to 90: analysis of the causes of the observed sex differences in brain metabolites.

RATIONALE AND OBJECTIVES: To assess whether differences in cerebral atrophy and white matter lesions or in the presence of lactate and lipid signals can explain the observed differences in brain choline, creatine, and N-acetylaspartate levels between healthy elderly women and men. METHODS: In addition to standard magnetic resonance imaging of the brain, an 8 x 8 x 2-cm3 supraventricular transverse brain volume parallel to the canthomeatal line was examined by magnetic resonance spectroscopy (automated 1H chemical shift imaging) in 540 healthy elderly persons. RESULTS: At P = 0.01, 0.001, and 0.0001, choline differed between women and men in 14, 9, and 5 of 36 voxels, respectively. On correction for cerebral atrophy (more frequent in men than in women), white matter lesions (more frequent in women), and lactate and lipid (more frequent in women), the differences in choline were reduced to 13, 6, and 3. Sex differences for creatine and N-acetylaspartate were similar but less numerous after correction. CONCLUSIONS: Elderly women and men in the general population show differences in the levels of creatine, N-acetylaspartate, and especially choline in portions of the brain. The sex-related differences in brain metabolite levels cannot be explained by differences in cerebral atrophy or other aging-related phenomena (white matter lesions, lactate, lipid).

31P-NMR spectroscopy and the metabolic properties of different muscle fibers.

To study the in vivo recruitment of different fiber types and their metabolic properties, 31P-nuclear magnetic resonance spectroscopy (31P-NMRS) of the human calf muscle was performed in seven normal sedentary subjects. In the exhaustive exercise protocol used, the work load was increased every minute during 5 min. This resulted in a prominent split of the Pi resonance in all subjects, indicating pH compartmentation in the muscles studied. From the chemical shift of the Pi peaks relative to phosphocreatine (PCr) at the end of the exercise, intracellular pH (pHi) averaged 6.92 +/- 0.05 (SD) in compartment 1 and 6.23 +/- 0.15 in compartment 2. The recovery of both Pi resonances after exercise could be followed easily in five of these subjects. The recovery rate of the Pi peak is a good estimate of the oxidative metabolism at the end of the exercise. A monoexponential regression analysis showed that the mean initial recovery rate S0 was 2.49 +/- 0.17%/s in compartment 1 and only 0.87 +/- 0.12%/s in compartment 2, indicating aerobic function three times higher in compartment 1 at the end of exercise. The mean relative ATP fraction dropped significantly (P less than 0.001), from 20.0 +/- 1.0% of the total 31P signal integral before exercise to 14.0 +/- 1.6% at the end of exercise. The simultaneous visualization of two compartments, in good order, one with high pHi and fast recovery and another with low pHi and slow recovery, is rationalized by the different metabolic behavior of type I and II fibers in human calf muscle in response to exhaustive exercise. This study demonstrates that 31P-NMRS is an excellent noninvasive procedure to quantify aerobic metabolism in both fiber types simultaneously.

Value of single-voxel proton MR spectroscopy in temporal lobe epilepsy.

PURPOSE: To study the value of different parameters derived from single-voxel proton MR spectroscopy of the mesial temporal lobes in the lateralization of the epileptogenic zone in patients with temporal lobe epilepsy. METHODS: We studied 12 healthy volunteers and 21 patients with temporal lobe epilepsy refractory to medical treatment, which was clearly lateralized with electroencephalography (EEG) and MR imaging. The mesial temporal lobes were investigated with single-voxel proton MR spectroscopy using a point-resolved spectroscopic sequence with an echo time of 135 milliseconds. The normalized concentration of N-acetylaspartate (NAA), creatine (Cr), and choline-containing compounds (Cho), and the metabolite ratios NAA/Cho+Cr, NAA/Cr, Cho/Cr, and NAA/Cho were calculated from the spectra. Using these values and an asymmetry index, we assigned the patients to one of five lateralization categories. RESULTS: The most consistent MR spectroscopic parameter for clear lateralization was the NAA/Cho+Cr ratio, followed by the NAA ratio. But with an adequate asymmetry index, the epilepsy in 17 (81%) of 21 patients could be lateralized by EEG and MR imaging with both parameters concordantly. Symmetric bilateral abnormalities were found in four of the 21 patients with NAA/Cho+Cr and in only one of the 21 patients with NAA. With both parameters, no contradictory lateralization was found; however, this was indeed the case with the remaining ratios, NAA/Cr, Cho/Cr, and NAA/Cho, in two, three, and one of the patients, respectively. A statistically significant decrease in NAA was found on the epileptic side, but also on the contralateral side. CONCLUSION: With an adequate asymmetry index, NAA/Cho+Cr and NAA are equally sensitive in predicting the side of involvement in patients with unilateral temporal lobe epilepsy.

An MR protocol for presurgical evaluation of patients with complex partial seizures of temporal lobe origin.

PURPOSE: To find an optimal diagnostic protocol for the presurgical MR evaluation of patients with temporal lobe epilepsy. METHODS: MR imaging in 14 healthy subjects and 25 consecutive patients with temporal lobe epilepsy was performed in paracoronal sections perpendicular to the hippocampi with T1-weighted inversion recovery and T2 weighting. Volume measurements of the hippocampus/amygdala complex were performed and a multiecho sequence yielded T2-calculated images. RESULTS: Hippocampal disease was seen in 22 of 25 temporal lobe epilepsy patients on paracoronal T1-weighted inversion recovery images. Four had bilateral abnormalities. Characteristic for hippocampal disease were features such as volume loss, decreased signal, and loss of internal morphology. Only 17 of 25 patients demonstrated hippocampal pathology on T2-weighted images, and in one patient this was bilateral. Patients with only minimal structural loss on T1-weighted inversion recovery had normal T2-weighted images. T2 calculation was no more sensitive than visual assessment on the T2-weighted images. Volume measurements were normal in one patient and misleading in two patients. Lateralization, as compared with clinical and electroencephalographic findings, was most confidently done with paracoronal T1-weighted inversion recovery images and volume measurements. CONCLUSIONS: An optimum MR protocol for temporal lobe epilepsy patients is proposed. Its essential feature is that the hippocampus be evaluated by paracoronal T1-weighted inversion recovery images and volume measurements. T2-weighted imaging can be omitted.

Single-voxel proton MR spectroscopy and positron emission tomography for lateralization of refractory temporal lobe epilepsy.

PURPOSE: We compared the metabolic information obtained from single-voxel proton MR spectroscopy and positron emission tomography (PET) in patients with temporal lobe epilepsy. METHODS: Twenty-nine patients with temporal lobe epilepsy were screened for metabolic abnormalities with both proton MR spectroscopy and PET. Lateralization with MR spectroscopy was possible by using NAA/(Cho+Cr) and an asymmetry index. Hypometabolism as determined by PET was classified as typical or complex. RESULTS: Twenty-four (96%) of 25 patients whose seizure onset could be lateralized to one temporal lobe showed ipsilateral lateralization with either MR spectroscopy or PET, whereas concordant lateralization with both techniques was possible only in 14 (56%) of the 25 patients. MR spectroscopy showed 42 abnormal temporal lobes whereas PET showed only 25 lobes with decreased metabolism. All temporal lobes with hypometabolism at PET also had a low NAA/(Cho+Cr). Five patients (20%) with negative PET studies had seizures lateralized correctly with MR spectroscopy. CONCLUSION: Proton MR spectroscopy is more sensitive in depicting metabolic abnormalities than is PET in patients with temporal lobe epilepsy. Patients with negative PET studies will benefit from MR spectroscopy for the purpose of lateralization.

Artefacts in multi-echo T2 imaging for high-precision gel dosimetry: I. Analysis and compensation of eddy currents.

In BANG gel dosimetry, the spin-spin relaxation rate, R2 = I/T2, is related to the radiation dose that has been delivered to the gel phantom. R2 is calculated by fitting the pixel intensities of a set of differently T2-weighted base images. In gel dosimetry for radiotherapy, an accuracy of 5% in dose and 3 mm spatially, whichever is lower, is the objective. Therefore, possible sources of artefacts must be considered and dealt with. To obtain a set of base images a multiple spin-echo sequence is used. However, in a conventional MR scanner eddy currents will be provoked by switching the imaging gradients. As the eddy currents change in the course of the sequence, the net magnetization will be affected accordingly. Hence, eddy currents may have a significant influence on the quantitative R2 images themselves as well as on their slice position. In this study, we report an analysis of the eddy currents as they appear in the multiple spin-echo sequence. Eddy currents are measured using a frequency shift method resulting in eddy current field maps. The related geometrical displacements are obtained by use of a pyramidal phantom. The R2 versus dose relation is determined in the three main directions of the magnet, revealing a dependence of the measured R2 on slice orientation. The time course of eddy currents is then used in a computer simulation to estimate the effects they produce in the recorded R2 images. A compensation method for eddy current effects in multi-echo T2 mapping is described.

Artefacts in multi-echo T2 imaging for high-precision gel dosimetry: II. Analysis of B1-field inhomogeneity.

In BANG gel dosimetry, the spin-spin relaxation rate, R2 = 1/T2, is related to radiation dose that has been delivered to a gel phantom. R2 is calculated by fitting the pixel intensities of a set of differently T2-weighted base images. The accuracy that is aimed for in this quantitative MR application is about 5% relative to the maximum dose. In a conventional imaging MR scanner, however, several imaging artefacts may perturb the final dose map. These deviations manifest themselves as either a deformation of the dose map or an inaccuracy of the dose pixel value. Inaccuracies in the dose maps are caused by both spatial and temporal deviations in signal intensities during scanning. This study deals with B1-field inhomogeneities as a source of dose inaccuracy. First, the influence of B1-field inhomogeneities on slice profiles is investigated using a thin-slice phantom. Secondly, a FLASH sequence is used to map the B1-field by assessing the effective flip angle in each voxel of a homogeneous phantom. In addition, both experiments and computer simulations revealed the effects of B1 field inhomogeneities on the measured R2. This work offers a method to correct R2 maps for B1 -field inhomogeneities.

An investigation of the chemical stability of a monomer/polymer gel dosimeter.

The aim of this work is to investigate the temporal stability of a polyacrylamide gelatin hydrogel used for 3D monomer/polymer gel dosimetry techniques involving different methods of analysis. Long-term instabilities for a similar gel have recently been reported, but differ markedly from those described in this work. Two kinds of long-term instabilities are described. One affects the slope of the dose-R2 plot and is related to post-irradiation polymerization of the comonomer/polymer aggregates. It is observed that post-irradiation polymerization only lasts 12 hours after irradiation. The other instability affects the intercept of the dose-R2 plot, lasts for up to 30 days and is related to the gelation process of gelatin. Further studies were performed on gelatin gels of varying compositions to obtain a better understanding of the molecular mechanism that causes the instability due to gelation. The studies included observations of the spin-spin and spin-lattice relaxation rates in combination with diffusion measurements and optical measurements. It is shown that the heating history during the manufacture of the gel affects the absolute R2 value of the gel but not its variation. The findings presented in this study may help in producing more stable and reproducible monomer/polymer gel dosimeters.

Validation and application of polymer gel dosimetry for the dose verification of an intensity-modulated arc therapy (IMAT) treatment.

Polymer gel dosimetry was used to assess an intensity-modulated arc therapy (IMAT) treatment for whole abdominopelvic radiotherapy. Prior to the actual dosimetry experiment, a uniformity study on an unirradiated anthropomorphic phantom was carried out. A correction was performed to minimize deviations in the R2 maps due to radiofrequency non-uniformities. In addition, compensation strategies were implemented to limit R2 deviations caused by temperature drift during scanning. Inter- and intra-slice R2 deviations in the phantom were thereby significantly reduced. This was verified in an investigative study where the same phantom was irradiated with two rectangular superimposed beams: structural deviations between gel measurements and computational results remained below 3% outside high dose gradient regions; the spatial shift in those regions was within 2.5 mm. When comparing gel measurements with computational results for the IMAT treatment, dose deviations were noted in the liver and right kidney, but the dose-volume constraints were met. Root-mean-square differences between both dose distributions were within 5% with spatial deviations not more than 2.5 mm. Dose fluctuations due to gantry angle discretization in the dose computation algorithm were particularly noticeable in the low-dose region.

Traumatic dissection of the internal carotid artery as unusual cause of hypoglossal nerve dysfunction.

A dissection of the internal carotid artery (ICA) in a 50-year-old man with hypoglossal nerve dysfunction is reported. This case illustrates how non-invasive imaging techniques, such as computed tomography and magnetic resonance angiography, can demonstrate this unusual etiology.

Pancreatic encephalopathy. A case report and review of the literature.

Pancreatic encephalopathy is an uncommon condition found in patients with acute pancreatitis. The present report shows the interest of MRI in the diagnosis of this disorder. Patchy white matter signal abnormalities, resembling plaques seen in multiple sclerosis, may reflect the lesions that are found in the cerebral white matter of post-mortem confirmed cases.

A large intracranial xanthoma in familial hypercholesterolemia.

Intracranial xanthomata occurring in patients with familial hypercholesterolemia are very rare. We present a young woman with a large intracranial xanthoma. The patient was treated for a familial hyperlipoproteinemia type IIa. MRI and morphological features are shown and discussed on reviewing the literature.