Challenges with hippocampal MR spectroscopy as a surrogate for pre-radiotherapy assessment of neurocognitive impairment in patients with brain metastasis.

AIM: Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF). METHODS: 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs. RESULTS: HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051). CONCLUSION: Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.

Hippocampal subfield volumetric changes after radiotherapy for brain metastases.

Background: Changes in the hippocampus after brain metastases radiotherapy can significantly impact neurocognitive functions. Numerous studies document hippocampal atrophy correlating with the radiation dose. This study aims to elucidate volumetric changes in patients undergoing whole-brain radiotherapy (WBRT) or targeted stereotactic radiotherapy (SRT) and to explore volumetric changes in the individual subregions of the hippocampus. Method: Ten patients indicated to WBRT and 18 to SRT underwent brain magnetic resonance before radiotherapy and after 4 months. A structural T1-weighted sequence was used for volumetric analysis, and the software FreeSurfer was employed as the tool for the volumetry evaluation of 19 individual hippocampal subregions. Results: The volume of the whole hippocampus, segmented by the software, was larger than the volume outlined by the radiation oncologist. No significant differences in volume changes were observed in the right hippocampus. In the left hippocampus, the only subregion with a smaller volume after WBRT was the granular cells and molecular layers of the dentate gyrus (GC-ML-DG) region (median change -5 mm3, median volume 137 vs. 135 mm3; P = .027), the region of the presumed location of neuronal progenitors. Conclusions: Our study enriches the theory that the loss of neural stem cells is involved in cognitive decline after radiotherapy, contributes to the understanding of cognitive impairment, and advocates for the need for SRT whenever possible to preserve cognitive functions in patients undergoing brain radiotherapy.

Preoperative percutaneous Onyx embolization of carotid body paragangliomas with balloon test occlusion.

Objectives: The study aims to analyze our first experience with direct percutaneous embolization of carotid body tumors (CBTs) using ethylene-vinyl alcohol copolymer (Onyx) along with balloon test occlusion (BTO). Methods: A retrospective preliminary single-center study was conducted at the Otorhinolaryngology and Head and Neck Surgery Department and the Medical Imaging Department of the University Teaching Hospital. A consecutive series of three patients with CBTs was treated at the local institution between October 2018 and June 2019. All three patients underwent preoperative percutaneous embolization using ethylene-vinyl alcohol copolymer (Onyx 18) with the addition of BTO. Outcome measures were the percentage of tumor devascularization, intraoperative blood losses, and operation times. BTO was evaluated by clinical neurological examination and neurosonological transcranial Doppler examination of the middle cerebral artery (MCA). Results: Devascularization of all three tumors was complete or near complete. All three tumors were surgically extirpated with excellent surgical outcomes. The blood losses were minimal, and the average operation time was 2 h and 8 min. BTO was positive in one patient, which was valuable additional information on carotid branches ligation limitations. The other two patients showed negative BTOs with the result of safety of eventual carotid arteries ligations. Conclusion: Preoperative direct percutaneous embolization of CBT with Onyx is a highly effective procedure that significantly facilitates surgery. BTO provides valuable additional information on the most appropriate and safe surgical approach.

Single-Centre Experience with Patients Selection for Mechanical Thrombectomy Based on Automated Computed Tomography Perfusion Analysis-A Comparison with Computed TomographyCT Perfusion Thrombectomy Trials.

BACKGROUND: In randomized clinical trials, mechanical thrombectomy (MT) was proved to be a highly effective treatment of acute ischemic stroke which improved clinical outcomes. Some of the trials used automated computed tomography perfusion (CTP) analysis for selection of participants. We present a single-center experience with CTP selection and comparison with CTP trials. METHODS: Data of consecutive MT patients (from January 2016 to December 2017) were retrospectively reviewed. All patients with multiphase CT angiography confirmed the presence of anterior circulation large vessel occlusion/s in the intracranial internal carotid artery and/or middle cerebral artery (M1 or M2) and with admission brain CTP analyzed by RAPID software were included into the analysis. RESULTS: Sixty-two patients fulfilled the inclusion criteria (mean age was 70.1 ± 13.6 years, females 48.5%). At baseline, National Institutes of Health Stroke Scale score was 16 (IQR = 13-20), Alberta Stroke Program Early CT Score (ASPECTS) was 8 (IQR = 7-9), CTP core volume was 20 mL (IQR = 2-36), and CTP penumbra volume was 145.5 mL (IQR = 107-184). Time from stroke onset to imaging was 1 hour 32 minutes, time from stroke onset to reperfusion was 3 hours 50 minutes, and median time from CT to reperfusion was 1 hour 56 minutes. Modified thrombolysis in cerebral infarction 2b/3 was achieved in 42 patients (67.7%). Twenty-three patients (37%) had modified Rankin scale 0-2 at 90 days. CONCLUSIONS: Our analysis of CTP-selected patients for MT supports clinical applicability of automated CTP analysis into everyday clinical practice.

Incidence of Hippocampal Metastases: Laterality and Implications for Unilateral Hippocampal Avoiding Whole Brain Radiotherapy.

INTRODUCTION: Hippocampi sparing whole brain radiotherapy (WBRT) is an evolving approach in the treatment of patients with multiple brain metastases, pursuing mitigation of verbal memory decline as a consequence of hippocampal radiation injury. Accumulating data are showing different postradiotherapy changes in the left and right hippocampus with a theoretical proposal of only unilateral (dominant, left) hippocampal sparing during WBRT. METHOD: The aim of this retrospective study is to describe spatial distribution of brain metastases on MRI in a cohort of 260 patients (2595 metastases) and to evaluate distribution separately in the left and right hippocampus and in respective hippocampal avoiding zones (HAZ, region with subtherapeutic radiation dose), including evaluation of location of metastatic mass centre. RESULTS: The median number of brain metastases was three, with lung cancer being the most common type of primary tumour; 36% had single metastasis. Almost 8% of patients had metastasis within hippocampus (1.1% of all metastases) and 18.1% of patients within HAZ (3.3% of all metastases). No statistically significant difference was observed in the laterality of hippocampal involvement, also when the location of centre of metastases was analyzed. There were more patients presenting the centre of metastasis within left (15) versus right (6) HAZ approaching the borderline of statistical significance. CONCLUSION: No significant difference in the laterality of BM seeding within hippocampal structures was observed. The hypothesized unilateral sparing WBRT would have theoretical advantage in about 50% reduction in the risk of subsequent recurrence within spared regions.

Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study.

BACKGROUND AND PURPOSE: The aim of this prospective study is to evaluate post-whole brain radiotherapy (WBRT) changes in hippocampal concentration of N-acetylaspartate (h-tNAA) as a marker of neuronal loss and to correlate those changes to neurocognitive function. MATERIAL AND METHODS: Thirty-five patients with brain metastases underwent baseline single slice multi-voxel MR spectroscopy (MRS) examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory (Auditory Verbal Learning Test and Brief Visuospatial Memory Test - Revised) as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Eighteen patients completed follow-up evaluation four months after standard WBRT (2 laterolateral fields, 10×3.0Gy, 6MV photons) and were included in this analysis. MRS and cognitive examinations were repeated and compared to baseline measurements. RESULTS: Statistically significant decreases in h-tNAA were observed in the right (8.52-7.42mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60mM; -12%, 95%CI: -7.9 to -16.2%). Statistically significant decline was observed in all AVLT and BVMT-R subtests with exception of AVLT_Recognition. Quality of life declined after WBRT (mean Δ -14.1±20.3 points in transformed 0-100 point scale; p=0.018) with no correlation to changes in hippocampal metabolite concentrations. Moderate positive correlation was observed between left h-tNAA concentration decrease and AVLT_TR decline (r=+0.32; p=0.24) as well as with AVLT_DR (r=+0.33; p=0.22) decline. Changes in right h-tNAA/Cr negatively correlated with AVLT_DR (r=-0.48; p=0.061). No correlation between right hippocampus h-tNAA and memory decline (AVLT) was observed. CONCLUSIONS: Our results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.

Advanced MRI increases the diagnostic accuracy of recurrent glioblastoma: Single institution thresholds and validation of MR spectroscopy and diffusion weighted MR imaging.

The accurate identification of glioblastoma progression remains an unmet clinical need. The aim of this prospective single-institutional study is to determine and validate thresholds for the main metabolite concentrations obtained by MR spectroscopy (MRS) and the values of the apparent diffusion coefficient (ADC) to enable distinguishing tumor recurrence from pseudoprogression. Thirty-nine patients after the standard treatment of a glioblastoma underwent advanced imaging by MRS and ADC at the time of suspected recurrence - median time to progression was 6.7 months. The highest significant sensitivity and specificity to call the glioblastoma recurrence was observed for the total choline (tCho) to total N-acetylaspartate (tNAA) concentration ratio with the threshold ≥ 1.3 (sensitivity 100.0% and specificity 94.7%). The ADCmean value higher than 1313 × 10(- 6) mm(2)/s was associated with the pseudoprogression (sensitivity 98.3%, specificity 100.0%). The combination of MRS focused on the tCho/tNAA concentration ratio and the ADCmean value represents imaging methods applicable to early non-invasive differentiation between a glioblastoma recurrence and a pseudoprogression. However, the institutional definition and validation of thresholds for differential diagnostics is needed for the elimination of setup errors before implementation of these multimodal imaging techniques into clinical practice, as well as into clinical trials.

The Diagnostic Ability of Follow-Up Imaging Biomarkers after Treatment of Glioblastoma in the Temozolomide Era: Implications from Proton MR Spectroscopy and Apparent Diffusion Coefficient Mapping.

OBJECTIVE: To prospectively determine institutional cut-off values of apparent diffusion coefficients (ADCs) and concentration of tissue metabolites measured by MR spectroscopy (MRS) for early differentiation between glioblastoma (GBM) relapse and treatment-related changes after standard treatment. MATERIALS AND METHODS: Twenty-four GBM patients who received gross total resection and standard adjuvant therapy underwent MRI examination focusing on the enhancing region suspected of tumor recurrence. ADC maps, concentrations of N-acetylaspartate, choline, creatine, lipids, and lactate, and metabolite ratios were determined. Final diagnosis as determined by biopsy or follow-up imaging was correlated to the results of advanced MRI findings. RESULTS: Eighteen (75%) and 6 (25%) patients developed tumor recurrence and pseudoprogression, respectively. Mean time to radiographic progression from the end of chemoradiotherapy was 5.8 ± 5.6 months. Significant differences in ADC and MRS data were observed between those with progression and pseudoprogression. Recurrence was characterized by N-acetylaspartate ≤ 1.5 mM, choline/N-acetylaspartate ≥ 1.4 (sensitivity 100%, specificity 91.7%), N-acetylaspartate/creatine ≤ 0.7, and ADC ≤ 1300 × 10(-6) mm(2)/s (sensitivity 100%, specificity 100%). CONCLUSION: Institutional validation of cut-off values obtained from advanced MRI methods is warranted not only for diagnosis of GBM recurrence, but also as enrollment criteria in salvage clinical trials and for reporting of outcomes of initial treatment.

Hippocampal proton MR spectroscopy as a novel approach in the assessment of radiation injury and the correlation to neurocognitive function impairment: initial experiences.

BACKGROUND: The hippocampus is considered as the main radiosensitive brain structure responsible for postradiotherapy cognitive decline. We prospectively assessed correlation of memory change to hippocampal N-acetylaspartate (h-tNAA) concentration, a neuronal density and viability marker, by (1)H-MR spectroscopy focused on the hippocampus. METHODS: Patients with brain metastases underwent whole brain radiotherapy (WBRT) to a dose of 30 Gy in ten fractions daily. Pre-radiotherapy (1)H-MR spectroscopy focused on the h-tNAA concentration and memory testing was performed. Memory was evaluated by Auditory Verbal Learning Test (AVLT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Total recall, recognition and delayed recall were reported. The both investigation procedures were repeated 4 months after WBRT and the h-tNAA and memory changes were correlated. RESULTS: Of the 20 patients, ten passed whole protocol. The h-tNAA concentration significantly decreased from pre-WBRT 8.9, 8.86 and 8.88 [mM] in the right, left and both hippocampi to 7.16, 7.65 and 7.4 after WBRT, respectively. In the memory tests a significant decrease was observed in AVLT total-recall, BVMT-R total-recall and BVMT-R delayed-recall. Weak to moderate correlations were observed between left h-tNAA and AVLT recognition and all BVMT-R subtests and between the right h-tNAA and AVLT total-recall. CONCLUSIONS: A significant decrease in h-tNAA after WBRT was proven by (1)H-MR spectroscopy as a feasible method for the in vivo investigation of radiation injury. Continuing patient recruitment focusing on other cognitive tests and metabolites is needed.

Endoscopic drainage treatment of pancreatic pseudocysts.

BACKGROUND/AIMS: This study presents the experience of its authors with endoscopic drainage treatment of pancreatic pseudocysts. The first part of the study offers a literature overview of the basic knowledge of pancreatic pseudocysts. The authors gradually deal with the individual types of pancreatic pseudocysts, the clinical picture, complications and diagnostics. Within the bounds of differential diagnostics the authors stress mainly the necessity of differentiating pancreatic pseudocysts from cystic tumors and benign cysts. Special attention is dedicated to various modalities of pancreatic pseudocyst treatment. The second part of the study presents the authors' own results of the endoscopic drainage treatment of pancreatic pseudocysts. METHODOLOGY: Results of endoscopic drainage treatment of pancreatic pseudocysts, which is one of significant possibilities of treatment of these conditions, are presented. RESULTS: This method was used to treat 33 patients (24 men and 9 women) from September 2007 to March 2009. Endoscopic drainage of pancreatic pseudocysts was performed 4 times transduodenally a 29 times transgastrically, namely in 6 cases under endosonographic guidance and in 27 cases by a duodenoscope after endosonographic targeting. CONCLUSIONS: The authors conclude that endoscopic drainage is an effective method of pancreatic pseudocyst treatment.

Endoscopic drainage treatment of pancreatic pseudocysts.

BACKGROUND/AIMS: This study presents the experience of its authors with endoscopic drainage treatment of pancreatic pseudocysts. The first part of the study offers a literature overview of the basic knowledge of pancreatic pseudocysts. The authors gradually deal with the individual types of pancreatic pseudocysts, the clinical picture, complications and diagnostics. Within the bounds of differential diagnostics the authors stress mainly the necessity of differentiating pancreatic pseudocysts from cystic tumors and benign cysts. Special attention is dedicated to various modalities of pancreatic pseudocyst treatment. The second part of the study presents the authors' own results of the endoscopic drainage treatment of pancreatic pseudocysts. METHODOLOGY: Results of endoscopic drainage treatment of pancreatic pseudocysts, which is one of significant possibilities of treatment of these conditions, are presented. RESULTS: This method was used to treat 33 patients (24 men and 9 women) from September 2007 to March 2009. Endoscopic drainage of pancreatic pseudocysts was performed four times transduodenally and 29 times transgastrically, of which 6 cases were under endosonographic guidance and 27 cases by a duodenoscopy after endosonographic targeting. CONCLUSIONS: The authors conclude that endoscopic drainage is an effective method of pancreatic pseudocyst treatment.

Potential of MR spectroscopy for assessment of glioma grading.

BACKGROUND: Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids. METHODS: In this review, we describe potential of MRS for grading of gliomas. RESULTS: Low-grade gliomas are generally characterized by a relatively high concentration of N-acetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies. CONCLUSIONS: Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade.