Diagnostic accuracy of anti-3-[18F]-FACBC PET/MRI in gliomas.

PURPOSE: The primary aim was to evaluate whether anti-3-[18F]FACBC PET combined with conventional MRI correlated better with histomolecular diagnosis (reference standard) than MRI alone in glioma diagnostics. The ability of anti-3-[18F]FACBC to differentiate between molecular and histopathological entities in gliomas was also evaluated. METHODS: In this prospective study, patients with suspected primary or recurrent gliomas were recruited from two sites in Norway and examined with PET/MRI prior to surgery. Anti-3-[18F]FACBC uptake (TBRpeak) was compared to histomolecular features in 36 patients. PET results were then added to clinical MRI readings (performed by two neuroradiologists, blinded for histomolecular results and PET data) to assess the predicted tumor characteristics with and without PET. RESULTS: Histomolecular analyses revealed two CNS WHO grade 1, nine grade 2, eight grade 3, and 17 grade 4 gliomas. All tumors were visible on MRI FLAIR. The sensitivity of contrast-enhanced MRI and anti-3-[18F]FACBC PET was 61% (95%CI [45, 77]) and 72% (95%CI [58, 87]), respectively, in the detection of gliomas. Median TBRpeak was 7.1 (range: 1.4-19.2) for PET positive tumors. All CNS WHO grade 1 pilocytic astrocytomas/gangliogliomas, grade 3 oligodendrogliomas, and grade 4 glioblastomas/astrocytomas were PET positive, while 25% of grade 2-3 astrocytomas and 56% of grade 2-3 oligodendrogliomas were PET positive. Generally, TBRpeak increased with malignancy grade for diffuse gliomas. A significant difference in PET uptake between CNS WHO grade 2 and 4 gliomas (p < 0.001) and between grade 3 and 4 gliomas (p = 0.002) was observed. Diffuse IDH wildtype gliomas had significantly higher TBRpeak compared to IDH1/2 mutated gliomas (p < 0.001). Adding anti-3-[18F]FACBC PET to MRI improved the accuracy of predicted glioma grades, types, and IDH status, and yielded 13.9 and 16.7 percentage point improvement in the overall diagnoses for both readers, respectively. CONCLUSION: Anti-3-[18F]FACBC PET demonstrated high uptake in the majority of gliomas, especially in IDH wildtype gliomas, and improved the accuracy of preoperatively predicted glioma diagnoses. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04111588, URL: https://clinicaltrials.gov/study/NCT04111588.

Intraoperative 3D ultrasound-guided resection of diffuse low-grade gliomas: radiological and clinical results.

OBJECTIVE: Extent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)-guided resection under general anesthesia. METHODS: Consecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated. RESULTS: Forty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)-mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusion-weighted postoperative MRI. CONCLUSIONS: Three-dimensional US-guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

Intra-rater variability in low-grade glioma segmentation.

Assessment of size and growth are key radiological factors in low-grade gliomas (LGGs), both for prognostication and treatment evaluation, but the reliability of LGG-segmentation is scarcely studied. With a diffuse and invasive growth pattern, usually without contrast enhancement, these tumors can be difficult to delineate. The aim of this study was to investigate the intra-observer variability in LGG-segmentation for a radiologist without prior segmentation experience. Pre-operative 3D FLAIR images of 23 LGGs were segmented three times in the software 3D Slicer. Tumor volumes were calculated, together with the absolute and relative difference between the segmentations. To quantify the intra-rater variability, we used the Jaccard coefficient comparing both two (J2) and three (J3) segmentations as well as the Hausdorff Distance (HD). The variability measured with J2 improved significantly between the two last segmentations compared to the two first, going from 0.87 to 0.90 (p = 0.04). Between the last two segmentations, larger tumors showed a tendency towards smaller relative volume difference (p = 0.07), while tumors with well-defined borders had significantly less variability measured with both J2 (p = 0.04) and HD (p < 0.01). We found no significant relationship between variability and histological sub-types or Apparent Diffusion Coefficients (ADC). We found that the intra-rater variability can be considerable in serial LGG-segmentation, but the variability seems to decrease with experience and higher grade of border conspicuity. Our findings highlight that some criteria defining tumor borders and progression in 3D volumetric segmentation is needed, if moving from 2D to 3D assessment of size and growth of LGGs.

Incidental Intracranial Findings and Their Clinical Impact; The HUNT MRI Study in a General Population of 1006 Participants between 50-66 Years.

OBJECTIVES: Evaluate types and prevalence of all, incidental, and clinically relevant incidental intracranial findings, i.e. those referred to primary physician or clinical specialist, in a cohort between 50 and 66 years from the Nord-Trøndelag Health (HUNT) study. Types of follow-up, outcome of repeated neuroimaging and neurosurgical treatment were assessed. MATERIAL AND METHODS: 1006 participants (530 women) underwent MRI of the head at 1.5T consisting of T1 weighted sagittal IR-FSPGR volume, axial T2 weighted, gradient echo T2* weighted and FLAIR sequences plus time of flight cerebral angiography covering the circle of Willis. The nature of a finding and if it was incidental were determined from previous radiological examinations, patient records, phone interview, and/or additional neuroimaging. Handling and outcome of the clinically relevant incidental findings were prospectively recorded. True and false positives were estimated from the repeated neuroimaging. RESULTS: Prevalence of any intracranial finding was 32.7%. Incidental intracranial findings were present in 27.1% and clinically relevant findings in 15.1% of the participants in the HUNT MRI cohort. 185 individuals (18.4%) were contacted by phone about their findings. 40 participants (6.2%) underwent ≥ 1 additional neuroimaging session to establish etiology. Most false positives were linked to an initial diagnosis of suspected glioma, and overall positive predictive value of initial MRI was 0.90 across different diagnoses. 90.8% of the clinically relevant incidental findings were developmental and acquired cerebrovascular pathologies, the remaining 9.2% were intracranial tumors, of which extra-axial tumors predominated. In total, 3.9% of the participants were referred to a clinical specialist, and 11.7% to their primary physician. 1.4% underwent neurosurgery/radiotherapy, and 1 (0.1%) experienced a procedure related postoperative deficit. CONCLUSIONS: In a general population between 50 and 66 years most intracranial findings on MRI were incidental, and >15% of the cohort was referred to clinical-follow up. Hence good routines for handling of findings need to be in place to ensure timely and appropriate handling.

Repeated 3.0 Tesla Magnetic Resonance Imaging After Clinically Successful Lumbar Disc Surgery.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To describe the naturally occurring magnetic resonance imaging (MRI) findings after successful microsurgical removal of lumbar disc herniation with repeated MRI examinations. SUMMARY OF BACKGROUND DATA: The interpretation of MRI after spinal surgery may be particularly challenging and image findings do not always correlate to clinical findings. Early postoperative MRI has limited value in the evaluation of patients after surgery for lumbar disc herniation. METHODS: Prospective study of 30 successfully operated patients, which underwent 3.0 T MRI within 24 h after surgery for lumbar disc herniation and repeated at 6 weeks and 3 months postoperatively. Postoperative image findings (nerve root enhancement, nerve root thickening, displacement or compression of the nerve root, and residual mass size and signal) were assessed quantitatively. Inter-rater reliability was tested. RESULTS: Inter-rater reliability between neuroradiologists was moderate for assessed MRI variables. In the immediate postoperative phase, compression or dislocation of the nerve root at the operated level was common. A residual mass at the operated level was seen in 80%, 47%, and 33% after 24 h, 6 weeks, and 3 months, respectively. Postoperative dislocation or compression of the nerve root from residual masses was seen in 67%, 24%, and 14% after 24 h, 6 weeks, and 3 months, respectively. A residual mass with a higher signal than muscle on T2-weighted images was seen in 80%, 30%, and 17% after 24 h, 6 weeks, and 3 months, respectively. CONCLUSION: A residual mass with compression or dislocation of the nerve root at the operated level, that disappears over 3 months, is a common MRI finding in patients successfully operated for symptomatic lumbar disc herniation. An expectant approach instead of early reoperations may perhaps be preferred in patients with residual pain and root compression due to residual masses with high T2-signal since these often seem to resolve spontaneously. LEVEL OF EVIDENCE: 3.

Generalized epilepsy in a family with basal ganglia calcifications and mutations in SLC20A2 and CHRNB2.

BACKGROUND: The genetic understanding of primary familial brain calcification (PFBC) has increased considerably in recent years due to the finding of causal genes like SLC20A2, PDGFRB and PDGFB. The phenotype of PFBC is complex and has as of yet been poorly delineated. The most common clinical presentations include movement disorders, cognitive symptoms and psychiatric conditions. We report a family including two sisters with brain calcifications due to a variant in SLC20A2 and generalized tonic-clonic seizures as the principal phenotypic trait. METHODS: The affected siblings underwent whole exome sequencing and candidate variants and cosegregation in the family were validated by Sanger sequencing. RESULTS: Both siblings and their asymptomatic father were heterozygous for a variant in SLC20A2. The siblings also had a variant in CHRNB2, a known epilepsy gene associated with autosomal dominant frontal lobe epilepsy, which they had inherited from the mother. CONCLUSIONS: To our knowledge, the reported siblings represent the third and fourth subjects with confirmed SLC20A2 variants exhibiting epilepsy as a phenotypic trait. Our findings support seizures as part of the phenotypic spectrum of SLC20A2-related PFBC. However, the present phenotype may also result from additional genetic influence, such as the identified missense variant in CHRNB2.

Growth dynamics of untreated glioblastomas in vivo.

BACKGROUND: Glioblastomas are primary malignant brain tumors with a dismal prognosis. Knowledge of growth rates and underlying growth dynamics is useful for understanding basic tumor biology, developing realistic tumor models, and planning treatment logistics. METHODS: By using repeated pretreatment contrast-enhanced T1-weighted MRI scans from 106 patients (aged 26-83 years), we studied the growth dynamics of untreated glioblastomas in vivo. Growth rates were calculated as specific growth rates and equivalent volume doubling times. The fit of different possible growth models was assessed using maximum likelihood estimations. RESULTS: There were large variations in growth rates between patients. The median specific growth rate of the tumors was 1.4% per day, and the equivalent volume doubling time was 49.6 days. Exploring 3 different tumor growth models showed similar statistical fit for a Gompertzian growth model and a linear radial growth model and worse fit for an exponential growth model. However, large tumors had significantly lower growth rates than smaller tumors, supporting the assumption that glioblastomas reach a plateau phase and thus exhibit Gompertzian growth. CONCLUSION: Based on the fast growth rate of glioblastoma shown in this study, it is evident that poor treatment logistics will influence tumor size before surgery and can cause significant regrowth before adjuvant treatment. Since there is a known association between tumor volume, extent of surgical resection, and response to adjuvant therapy, it is likely that waiting times play a role in patient outcomes.

Acute endovascular repair of iatrogenic right internal carotid arterial laceration.

Carotid arterial bleeding is a feared and possible life-threatening complication of transsphenoidal surgery. We present a case of a meningioma that during resection had a serious complication with laceration of the internal carotid artery (ICA). These patients rarely undergo endovascular treatment, with indications mainly due to the development of pseudoaneurysms or penetrating trauma. However, endovascular treatment with covered stents of carotid arterial bleedings is a feasible alternative due to technical advances and smaller sized stentgrafts that expand treatment options.

Modic type I changes and recovery of back pain after lumbar microdiscectomy.

PURPOSE: To investigate whether the presence of Modic changes type I (MC I) found on preoperative MRI scans represent a risk factor for persistent back pain 12 months after surgery amongst patients operated for lumbar disc herniation. METHODS: Cohort study of 178 consecutive patients operated with lumbar microdiscectomy. Preoperative MRI scans were evaluated by two independent neuroradiologists. Primary outcome measure was the visual analogue scale (VAS) for back pain. Secondary outcome measures were; VAS for leg pain, physical function (Oswestry disability index), and health-related quality of life (EQ-5D), self-reported benefit of the operation and employment status. The presence of MC I was used as exposition variable and adjusted for other risk factors in multivariate analyses. RESULTS: The Modic classification showed a high inter-observer reproducibility. Patients with MC I had less improvement of back pain 12 months after surgery, compared to those who had no or other types of MC, but this negative association no longer showed statistical significance when adjusted for smoking, which remained the only independent risk factor for persistent back pain. CONCLUSIONS: Patients with preoperative MC I can expect less but still significant improvement of back pain 1 year after microdiscectomy, but not if they smoke cigarettes.

[Diagnostic imaging in neck and low back pain]. / Bildediagnostikk ved nakke- og ryggsmerter.

BACKGROUND: Diagnostic imaging in neck and low back pain can confirm serious pathology, but the clinical significance of findings is often unknown. Indications for diagnostic imaging in these patients are presented and the significance of common findings is discussed. MATERIAL AND METHODS: The review is based mainly on Norwegian guidelines (evidence-based) on low back pain, other selected publications, and a non-systematic PubMed-search for systematic reviews and randomised controlled trials of imaging in neck or low back pain. RESULTS: Routine imaging in neck or back pain is not documented to improve patient outcomes and we therefore advise against it. Imaging is indicated when serious conditions are suspected and should be considered for symptoms that have not improved after 4-6 weeks. Of the imaging modalities available, MRI has the highest sensitivity for most important disorders in the neck and back. Degenerative changes in vertebrae and intervertebral discs (including disc herniations) are common also in asymptomatic individuals and usually have uncertain relation to pain. Some MRI findings in bone marrow (so called Modic-changes) are more frequent among patients with low back pain, but their relevance to treatment is not clarified. INTERPRETATION: Imaging (usually MRI) in neck or back pain is only recommended for suspected serious conditions or clear symptoms that have not improved after 4-6 weeks. Degenerative changes seldom explain symptoms or influence treatment.

Functional magnetic resonance imaging and diffusion tensor tractography incorporated into an intraoperative 3-dimensional ultrasound-based neuronavigation system: impact on therapeutic strategies, extent of resection, and clinical outcome.

BACKGROUND: Functional neuronavigation with intraoperative 3-dimensional (3D) ultrasound may facilitate safer brain lesion resections than conventional neuronavigation. OBJECTIVE: In this study, functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) were used to map eloquent areas. We assessed the use of fMRI and DTT for preoperative assessments and determined whether using these data together with 3D ultrasound during surgery enabled safer lesion resection. METHODS: We reviewed 51 consecutive patients with intracranial lesions in whom fMRI with or without DTT was used to map eloquent areas. To assess a possible impact of fMRI/DTT, we reviewed and analyzed the quality of the fMRI/DTT data, any change in therapeutic strategies, lesion to eloquent area distance (LEAD), extent of resection, and clinical outcome. RESULTS: As a result of the fMRI/DTT mapping, the therapeutic strategies were changed in 4 patients. The median tumor residue for glioma patients was 11% (n = 33) and 0% for nonglioma lesions (n = 12). For gliomas, there was a significant correlation between decreasing LEAD and increasing tumor residue. Of the glioma patients, 42% underwent gross total resection (>or= 95%) and 12% suffered neurological worsening after surgery as a result of complications. Of glioma patients with an LEAD of

Sensitivity of MRI versus conventional screening in the diagnosis of BRCA-associated breast cancer in a national prospective series.

We wanted to compare the sensitivities of breast magnetic resonance imaging (MRI) and the conventional screening programme consisting of mammography (XRM) +/- ultrasound for early diagnosis of breast cancer in BRCA1/2 mutation carriers. BRCA1/2 mutation carriers were examined prospectively by both breast MRI and XRM +/- ultrasound. Eight hundred and sixty-seven MRI examinations were carried out in 445 BRCA1 and 46 BRCA2 mutation carriers. A total of 25 cancers were observed, five (20%) as interval cancers. At the time of diagnosis, sensitivity to detect cancer was 19/22=86% for MRI and 12/24=50% for XRM. Twenty-one were examined by both methods at the time of diagnosis. In the19 BRCA1 mutation carriers among them, MRI had a sensitivity of 1/3(33%) to diagnose DCIS and 15/16 (94%) among the invasive cancers. For XRM the sensitivities were 1/3(33%) for DCIS, 3/7(42%) for pT1b, 3/6(50%) for pT1c, and 3/3/100%) for pT2. In the two BRCA2 mutation carriers, both were demonstrated by breast MRI, neither was detected by XRM. Breast MRI had increased sensitivity compared to XRM to diagnose all cancers staged less than pT2.

[Chronic whiplash syndrome is no indication for craniocervical fixation]. / Kronisk nakkeslengsyndrom er ingen indikasjon for kraniocervikal fiksasjon.

Throughout many years, a large number of publications have focused on structural changes in soft tissues in the cervical spine in patients with whiplash associated disorders I-II. In recent years the development in MRI techniques have made it possible to visualize the small ligaments in the craniocervical junction; a small number of publications have investigated the association between signal changes in these ligaments and whiplash associated disorders I-II. The results are, however, not conclusive, and no prospective studies have demonstrated any causal connection between type of whiplash injury and signal changes in these ligaments. Craniocervical fixation is major surgery with a moderate level of perioperative complications. There is also a theoretical risk of increasing the degenerative process in the level below the fixation. The indications for craniocervical fixation are now serious conditions like instability caused by rheumatic arthritis, tumours and fractures. The scientific evidence for introducing a new indication for craniocervical fixation is lacking, and craniocervical fixation in WAD I-II must be considered experimental surgery.

Preoperative blood oxygen level-dependent functional magnetic resonance imaging in patients with primary brain tumors: clinical application and outcome.

OBJECTIVE: This study sought to evaluate the ability of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to successfully identify functional cortical areas in patients with primary brain tumors, to evaluate the use of the fMRI results in presurgical planning, and to assess the functional outcome of the patients with respect to the functional maps obtained with fMRI. METHODS: The study included 25 consecutive preoperative fMRI sessions in patients with primary brain tumors in or near sensorimotor and/or language cortices. All fMRI paradigms were analyzed and rated according to the degree of success. Several distances between tumor and functional cortex as delineated with BOLD fMRI were measured to assess the topographic relationship between these two structures. Pre- and postoperative neurological statuses were obtained from the patients' journals. RESULTS: Acquisition of BOLD fMRI images was successful in 80% of the cases. The primary cause of unsuccessful fMRI was echo-planar imaging signal voids that were the result of previous craniotomy; the secondary cause was excessive motion. The neurosurgeons used the fMRI results for preoperative planning in 75% of the cases in which fMRI was successful. The risk of postoperative loss of function tested with fMRI was significantly lower when the distance between tumor periphery and BOLD activity was 10 mm or more. CONCLUSION: The majority of patients with primary brain tumors were capable of satisfactorily performing the fMRI paradigms, and the information obtained was used in the preoperative planning. A distance of 10 mm or more between the functional cortex, as delineated with fMRI, and the tumor significantly reduced the risk of postoperative loss of function.

Quantification of breast tumor microvascular permeability with feruglose-enhanced MR imaging: initial phase II multicenter trial.

PURPOSE: To investigate use of the macromolecular contrast agent feruglose for differentiating and grading of human benign and malignant breast tumors on the basis of their microvascular characteristics. MATERIALS AND METHODS: Sixty-three women with 63 primary breast lesions were examined with dynamic T1-weighted gradient-echo magnetic resonance (MR) imaging after intravenous injection of feruglose. A two-compartment unidirectional kinetic model applied to the dynamic data yielded estimates of the endothelial transfer coefficient, KPS, and the fractional plasma volume of the tumors. These MR imaging-derived parameters were correlated with the histologic tumor grade and quantified according to the Scarff-Bloom-Richardson (SBR) score by means of Pearson product moment correlation analyses. Differences between malignant and nonmalignant breast lesions with respect to KPS for feruglose were evaluated by means of the chi2 test and by calculating the sensitivity, specificity, and positive and negative predictive values. RESULTS: Histologic analysis revealed 26 benign and 37 malignant tumors. A moderate yet statistically significant correlation between KPS and SBR score was found (R = 0.496, P <.001). No significant correlation was observed between fractional plasma volume and SBR score (R = 0.085, P =.507). The KPS values were zero for 19 (73%) of the 26 benign tumors and were greater than zero for 27 (73%) of the 37 carcinomas. This distribution was significantly different (chi2 = 13.035, P =.001). With the criterion KPS > 0 in carcinomas, sensitivity was 0.73, specificity was 0.73, and the positive predictive value was 0.79. CONCLUSION: Quantitative measures of tumor microvascular permeability can be used for breast tumor characterization. The probability of breast tumor microvascular hyperpermeability to be associated with malignancy is 79%.

[In vivo magnetic resonance spectroscopy]. / In vivo magnetisk resonansspektroskopi.

Magnetic resonance tomography (MR) has become a highly useful tool for diagnostic imaging. The technology is in a process of rapid development with new and better methods emerging for the imaging of anatomic and pathologic aspects. With some additional equipment, the MR instrument may also be used for in vivo magnetic resonance spectroscopy (MRS). In vivo MRS provides biochemical information about metabolites in a given tissue volume. This type of biochemical information can be extracted from volumes the size of a sugar lump within a recording period of about five minutes. New technologies also allow extracting such information from several volumes during one recording in which the information is processed as metabolic pictures. The method has found clinical applications in several fields, including the evaluation of brain tumours and epilepsy. The use of in vivo MRS will probably increase in the years ahead, especially, perhaps, for the follow-up of various therapeutic regimens. All suppliers of MR equipment now provide in vivo MRS sets and routines for recording and data analysis have become very user-friendly.