Impact of metabolic syndrome on postoperative outcomes of transsphenoidal pituitary surgery: analysis of U.S. nationwide inpatient sample data 2005-2018.

Introduction: Transsphenoidal surgery (TSS) is the preferred surgical method for most pituitary adenomas owing to high efficacy and low mortality. This study aimed to evaluate the influence of metabolic syndrome (MetS) on postoperative outcomes of TSS for pituitary adenoma. Methods: This population-based, retrospective observational study extracted data of adults 20-79 y receiving TSS for pituitary adenoma from the US Nationwide Inpatient Sample (NIS) between 2005-2018. Primary outcomes were pituitary-related complications, poor outcomes (i.e., in-hospital mortality or unfavorable discharge), prolonged length of stay (LOS), and patient safety indicators (PSIs). Univariate and multivariate regressions were performed to determine the associations between study variables and outcomes. Results: 19,076 patients (representing a 93,185 US in-patient population) were included, among which 2,109 (11.1%) patients had MetS. After adjustment, pre-existing MetS was not significantly associated with presence of pituitary-related complications and poor outcomes. In contrast, MetS was significantly associated with an increased risk for prolonged LOS (adjusted OR (aOR) = 1.19; 95% CI: 1.05-1.34), PSIs (aOR = 1.31; 95% CI: 1.07-1.59) and greater hospital costs (adjusted ß = 8.63 thousand USD; 95% CI: 4.98-12.29). Among pituitary-related complications, MetS was independently associated with increased risk of cerebrospinal fluid (CSF) rhinorrhea (aOR = 1.22, 95% CI: 1.01, 1.47) but lowered diabetes insipidus (aOR = 0.83, 95% CI: 0.71, 0.97). Discussion: MetS does not pose excessive risk of in-hospital mortality or unfavorable discharge. However, MetS independently predicted having PSIs, prolonged LOS, greater hospital costs, and CSF rhinorrhea. Study findings may help clinicians achieve better risk stratification before TSS.

The impact of surgeon's academic leave on surgical outcomes for endoscopic transsphenoidal resection of pituitary tumors.

Background: Endoscopic surgery has become the mainstay of pituitary surgery, but requires comprehensive surgical training. We evaluate the impact of a surgeon's academic leave during endoscopic training on surgical outcomes of patients with pituitary tumors. Methods: This retrospective study reviewed the surgical outcomes of endoscopic transsphenoidal surgery for pituitary tumors performed by a single surgeon. The last 56 surgical cases were performed between July 2010 and August 2014 before academic leave (Phase 1 surgery group), while another 56 consecutive cases were performed between November 2017 and March 2020 immediately after the surgeon's academic leave (Phase 2 surgery group). Demographic and clinical characteristics were collected and compared between the two surgery groups. Results: Overall, most surgical outcomes of endoscopic transsphenoidal surgery were not affected adversely by the period of academic leave. The operative time and length of hospital stay was lower in the Phase 2 surgery group compared to the Phase 1 surgery group (P<0.05). Postoperative tumor residual, intraoperative cerebrospinal fluid (CSF) leaks and reoperation also decreased significantly in the Phase 2 group compared to the Phase 1 group (P<0.05). Similar results were observed in patients operated using a one-hand/mono-nostril and two-hand/one-and-half nostril technique. Conclusions: Academic leave had no negative impact on most surgical outcomes for endoscopic transsphenoidal resection of pituitary tumors. Moreover, a trend toward shorter operative times and length of hospital stays was noted for patients receiving surgery immediately after surgeon's return from leave.

Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005-2018.

Background: This retrospective study aimed to determine the risk of venous thromboembolism (VTE) in patients with PsA after surgery for lumbar degenerative disease (LDD). Methods: The study data of adults aged ≥20 years admitted to U.S. hospitals with diagnoses of LDD and undergoing spinal decompression or fusion between 2005 and 2018 were extracted from the National Inpatient Sample (NIS) database. Patients were further divided into two groups based on a diagnosis of PsA or not via codes ICD-9: 696.0 and ICD-10: L40.50. Patients with missing information were excluded. Propensity score matching (PSM) was employed to enhance comparability between groups. Logistic regression was used to determine associations between PsA and various outcomes, including complications, unfavorable discharge, and prolonged length of stay (LOS). Results: Data on 471,283 patients with LDD was extracted from the NIS database.from 2005 to 2018. Before propensity score matching, patients with PsA had higher proportions of overall morbidity (8.8 % vs. 6.9 %), VTE (1.4 % vs. 0.7 %), and unfavorable discharge (20.8 % vs. 16.9 %). After matching, patients with PsA still had higher VTE incidence and unfavorable discharge proportions. After adjustments, multivariable regression analysis indicated that patients with PsA had a higher risk of unfavorable discharge (aOR: 1.26, 95 % CI: 1.03-1.55) and VTE (aOR: 1.99, 95 % CI: 1.05-3.75). Conclusions: Among patients undergoing surgery for LDD, pre-existing PsA may be associated with increased risks of unfavorable discharge and VTE occurrence. The findings may benefit preoperative risk stratifications before LDD surgeries.

Prognostic value of interim CT-based peritumoral and intratumoral radiomics in laryngeal and hypopharyngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND AND PURPOSE: We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC). MATERIALS AND METHODS: A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO-Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated. RESULTS: The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia. CONCLUSION: Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT.

Augmented Reality Surgical Navigation System Integrated with Deep Learning.

Most current surgical navigation methods rely on optical navigators with images displayed on an external screen. However, minimizing distractions during surgery is critical and the spatial information displayed in this arrangement is non-intuitive. Previous studies have proposed combining optical navigation systems with augmented reality (AR) to provide surgeons with intuitive imaging during surgery, through the use of planar and three-dimensional imagery. However, these studies have mainly focused on visual aids and have paid relatively little attention to real surgical guidance aids. Moreover, the use of augmented reality reduces system stability and accuracy, and optical navigation systems are costly. Therefore, this paper proposed an augmented reality surgical navigation system based on image positioning that achieves the desired system advantages with low cost, high stability, and high accuracy. This system also provides intuitive guidance for the surgical target point, entry point, and trajectory. Once the surgeon uses the navigation stick to indicate the position of the surgical entry point, the connection between the surgical target and the surgical entry point is immediately displayed on the AR device (tablet or HoloLens glasses), and a dynamic auxiliary line is shown to assist with incision angle and depth. Clinical trials were conducted for EVD (extra-ventricular drainage) surgery, and surgeons confirmed the system's overall benefit. A "virtual object automatic scanning" method is proposed to achieve a high accuracy of 1 ± 0.1 mm for the AR-based system. Furthermore, a deep learning-based U-Net segmentation network is incorporated to enable automatic identification of the hydrocephalus location by the system. The system achieves improved recognition accuracy, sensitivity, and specificity of 99.93%, 93.85%, and 95.73%, respectively, representing a significant improvement from previous studies.

Augmented Reality Surgical Navigation System for External Ventricular Drain.

Augmented reality surgery systems are playing an increasing role in the operating room, but applying such systems to neurosurgery presents particular challenges. In addition to using augmented reality technology to display the position of the surgical target position in 3D in real time, the application must also display the scalpel entry point and scalpel orientation, with accurate superposition on the patient. To improve the intuitiveness, efficiency, and accuracy of extra-ventricular drain surgery, this paper proposes an augmented reality surgical navigation system which accurately superimposes the surgical target position, scalpel entry point, and scalpel direction on a patient's head and displays this data on a tablet. The accuracy of the optical measurement system (NDI Polaris Vicra) was first independently tested, and then complemented by the design of functions to help the surgeon quickly identify the surgical target position and determine the preferred entry point. A tablet PC was used to display the superimposed images of the surgical target, entry point, and scalpel on top of the patient, allowing for correct scalpel orientation. Digital imaging and communications in medicine (DICOM) results for the patient's computed tomography were used to create a phantom and its associated AR model. This model was then imported into the application, which was then executed on the tablet. In the preoperative phase, the technician first spent 5-7 min to superimpose the virtual image of the head and the scalpel. The surgeon then took 2 min to identify the intended target position and entry point position on the tablet, which then dynamically displayed the superimposed image of the head, target position, entry point position, and scalpel (including the scalpel tip and scalpel orientation). Multiple experiments were successfully conducted on the phantom, along with six practical trials of clinical neurosurgical EVD. In the 2D-plane-superposition model, the optical measurement system (NDI Polaris Vicra) provided highly accurate visualization (2.01 ± 1.12 mm). In hospital-based clinical trials, the average technician preparation time was 6 min, while the surgeon required an average of 3.5 min to set the target and entry-point positions and accurately overlay the orientation with an NDI surgical stick. In the preparation phase, the average time required for the DICOM-formatted image processing and program import was 120 ± 30 min. The accuracy of the designed augmented reality optical surgical navigation system met clinical requirements, and can provide a visual and intuitive guide for neurosurgeons. The surgeon can use the tablet application to obtain real-time DICOM-formatted images of the patient, change the position of the surgical entry point, and instantly obtain an updated surgical path and surgical angle. The proposed design can be used as the basis for various augmented reality brain surgery navigation systems in the future.

Surgical Outcome and Evaluation of Strategies in the Management of Growth Hormone-Secreting Pituitary Adenomas After Initial Transsphenoidal Pituitary Adenectomy Failure.

Acromegaly is a systemic disease that requires multidisciplinary treatment to achieve the best clinical outcome. This study aimed to evaluate the outcomes of the endoscopic transsphenoidal approach (TSA) as the primary treatment for somatotroph adenomas and further investigate patients who had suboptimal surgical results. This retrospective study included 83 patients with somatotroph adenomas treated by TSA at our institution from 1999 to 2010. Biochemical remission was defined as hGH <1 and <2.5 ng/ml. Factors associated with failure of TSA and strategy of secondary treatments for refractory and recurrent disease were analyzed. The mean age of patients was 41.1 ± 11.3 years, and the mean follow-up time was 54.2 ± 44.3 months. Approximately 44.5% of patients had residual tumors after TSA. Larger tumor size, higher GH level before the operation, and the existence of residual tumors were associated with TSA failure. Forty-one patients had an inadequate response to TSA or a recurrent lesion, and of these patients, 37 had residual tumor after TSA. Octreotide results in good outcomes in the treatment of DGSA patients, and SRS/EXRT generates good results in treating patients who receive second treatments when remission cannot be reached 6 months after TSA operation.

Using a consensus acupoints regimen to explore the relationship between acupuncture sensation and lumbar spinal postoperative analgesia: A retrospective analysis of prospective clinical cooperation.

OBJECTIVE: This study evaluated the effectiveness of acupuncture treatment on postoperative pain in patients with degenerative lumbar spine disease, and explored the relationship between the postoperative analgesic effect of acupuncture and the sensation of acupuncture experienced by the patients. METHODS: This retrospective study analyzed the medical records of 97 patients who had undergone an operation by the same surgeon due to degenerative lumbar disease. These patients were divided into acupuncture group (n = 32), patient-controlled analgesia (PCA) group (n = 27), and oral analgesia group (n = 38) according to the different postoperative analgesic methods. During their hospitalization, patients completed daily evaluations of their pain using a visual analogue scale (VAS), and injection times of supplemental meperidine were recorded. Also, the Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS) was used in the acupuncture group. RESULTS: Each of the three treatment groups showed significant reductions in postoperative pain, as shown by reduced VAS scores. The acupuncture group, however, had less rebound pain (P < 0.05) than the other two groups. Both the acupuncture and PCA groups experienced acute analgesic effects that were superior to those in the oral analgesia group. In addition, the higher the C-MASS index on the second day after surgery, the lower the VAS score on the fourth day after surgery. There was also a significant difference in the "dull pain" in the acupuncture sensation. CONCLUSION: The results demonstrated that acupuncture was beneficial for postoperative pain and discomfort after simple surgery for degenerative spinal disease. It is worth noting that there was a disproportionate relevance between the patient's acupuncture sensation and the improvement of pain VAS score.

Survival after multiple nail gun injuries to the brain, lung, and heart: a case report and a review of the literature.

Most nail gun injuries involve the extremities and result from work-related accidents. Injuries to the brain or thorax are relatively rare, and cases with injuries to both regions are even rarer and often lethal. Initial evaluation, resuscitation, and surgical planning can be challenging for emergency physicians and surgeons. We present the details of a man with multiple nail gun injuries to the brain, lung, and heart following a suicide attempt. The patient presented to the emergency department in shock. After immediate resuscitation, emergent sternotomy, and subsequent craniotomy, he was discharged without significant morbidity. According to the literature, this is the only reported case involving multiple nail gun injuries to the brain, lungs, and heart. The mortality rate of multiple nail gun injuries involving the head and chest is approximately 20%. Rapid evaluation, immediate resuscitation, and appropriate imaging and surgery are crucial for increasing survival and achieving a good prognosis. Emergency sternotomy for cardiac injury is the foremost priority, and the timing of craniotomy depends on the patient's vital sign status and whether brain injury is evident.A preprint of this article is available online: DOI: 10.21203/rs.3.rs-35448/v1.

Endoscopic transsphenoidal surgery for resection of pituitary macroadenoma: A retrospective study.

BACKGROUND: The endoscopic transsphenoidal approach is an efficient minimally invasive procedure for removal of pituitary tumors that can be accomplished through a one-hand or two-hand approach. The one-hand procedure through one nostril is more intuitive for surgeons, but maneuvering the instruments can be restrictive. The two-hand procedure using a one-and-half nostril approach provides more precise manipulation. This study aimed to compare the surgical outcomes of one-hand/mono-nostril and two-hand/one-and-half nostril surgeries for resection of large pituitary tumors by a single neurosurgeon. MATERIALS AND METHODS: The surgical data of 78 consecutive cases with pituitary macroadenoma (diameter >1 cm) were reviewed retrospectively. Altogether, 30 cases received one-hand/mono-nostril surgery, while 48 cases received two-hand/one-and-half nostril surgery. Postoperative outcomes of the two operations were compared. RESULTS: The operative time, hospital stay, residual rate of pituitary macroadenoma, visual field, surgical complications, and re-operative rates were slightly improved in the two-hand/one-and-half nostril surgery group compared with that in the one-hand/mono-nostril surgery group (all p>0.05). However, postoperative hypopituitarism was less frequent (1/48; 2.0%) with the two-hand/one-and-half nostril approach than with the mono-nostril approach (p = 0.004). Similar surgical outcomes were found in all patients with either small or large pituitary tumors, except that the difference in postoperative improvement in visual field change reached statistical significance (p = 0.044). CONCLUSION: A single-surgeon endoscopic endonasal transsphenoidal surgery with two-hand/one-and-half nostril approach is an effective and safe procedure for removal of large pituitary tumors.

Aggressive cytoreduction and multiple subpial cortical transections may obtain good surgical outcomes in refractory epilepsy with multiple epileptic foci.

BACKGROUNDS: Epilepsy surgery is the most efficacious therapeutic modality for patients with medical refractory epilepsy, especially resective surgery. However, the variable etiologies and multiple epileptic foci are usually associated with the outcomes. The aim of this study was to demonstrate that combination of different intervention procedures might be an alternative option for patients of refractory epilepsy. METHODS: We retrospectively analyzed pre-operative and post-surgical outcomes in 30 patients who received epilepsy surgery between January 1, 2010 and December 31, 2014 at Chang Gung Memorial Hospital (CGMH), Linkou, according to Engel's classification. RESULTS: Twenty-six of the 30 patients (86.7%) had good outcomes, sum of class I and class II after epilepsy surgery. The good outcome rate of our complicated group was 80.0% (12/15), compared to 93.3% (14/15) in the simple group, but no significant differences between the two groups (p = 0.569). Four patients whose epileptic foci involved eloquent area and received multiple subpial cortical transection, and good outcome rate was 75% (3/4). At last, six patients had previously failed epilepsy surgery and received a reoperation, with a good outcome rate of 83.3% (5/6). CONCLUSION: After complete pre-surgical evaluation and combined interventional procedures, the patients with refractory epilepsy had satisfactory outcomes and few neurological complications. Moreover, re-operation can improve the outcome in some patients who previously failed epilepsy surgery.

A Neural Network Approach to Identify Glioblastoma Progression Phenotype from Multimodal MRI.

The phenotypes of glioblastoma (GBM) progression after treatment are heterogeneous in both imaging and clinical prognosis. This study aims to apply radiomics and neural network analysis to preoperative multimodal MRI data to characterize tumor progression phenotypes. We retrospectively reviewed 41 patients with newly diagnosed cerebral GBM from 2009-2016 who comprised the machine learning training group, and prospectively included 18 patients from 2017-2018 for data validation. Preoperative MRI examinations included structural MRI, diffusion tensor imaging, and perfusion MRI. Tumor progression patterns were categorized as diffuse or localized. A supervised machine learning model and neural network-based models (VGG16 and ResNet50) were used to establish the prediction model of the pattern of progression. The diffuse progression pattern showed a significantly worse prognosis regarding overall survival (p = 0.032). A total of 153 of the 841 radiomic features were used to classify progression patterns using different machine learning models with an overall accuracy of 81% (range: 77.5-82.5%, AUC = 0.83-0.89). Further application of the pretrained ResNet50 and VGG 16 neural network models demonstrated an overall accuracy of 93.1 and 96.1%. The progression patterns of GBM are an important prognostic factor and can potentially be predicted by combining multimodal MR radiomics with machine learning.

Three-Dimensional Volumetric Changes and Clinical Outcomes after Decompression with DIAM™ Implantation in Patients with Degenerative Lumbar Spine Diseases.

Background and objectives: The prevalence of degenerative lumbar spine diseases has increased. In addition to standard lumbar decompression and/or fusion techniques, implantation of interspinous process devices (IPDs) can provide clinical benefits in highly selected patients. However, changes in spinal structures after IPD implantation using magnetic resonance imaging (MRI) have rarely been discussed. This volumetric study aimed to evaluate the effect of IPD implantation on the intervertebral disc and foramen using three-dimensional assessment. Materials and Methods: We retrospectively reviewed patients with lumbar degenerative disc diseases treated with IPD implantation and foraminotomy and/or discectomy between January 2016 and December 2019. The mean follow-up period was 13.6 months. The perioperative lumbar MRI data were processed for 3D-volumetric analysis. Clinical outcomes, including the Prolo scale and visual analog scale (VAS) scores, and radiographic outcomes, such as the disc height, foraminal area, and translation, were analyzed. Results: Fifty patients were included in our study. At the one-year follow-up, the VAS and Prolo scale scores significantly improved (both p < 0.001). The disc height and foraminal area on radiographs also increased significantly, but with limited effects up to three months postoperatively. MRI revealed an increased postoperative disc height with a mean difference of 0.5 ± 0.1 mm (p < 0.001). Although the mean disc volume difference did not significantly increase, the mean foraminal volume difference was 0.4 ± 0.16 mm3 (p < 0.05). Conclusions: In select patients with degenerative disc diseases or lumbar spinal stenosis, the intervertebral foramen was enlarged, and disc loading was reduced after IPD implantation with decompression surgery. The 3D findings were compatible with the clinical benefits.

Publisher Correction: A Neural Network Approach to Identify the Peritumoral Invasive Areas in Glioblastoma Patients by Using MR Radiomics.

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

A Neural Network Approach to Identify the Peritumoral Invasive Areas in Glioblastoma Patients by Using MR Radiomics.

The challenge in the treatment of glioblastoma is the failure to identify the cancer invasive area outside the contrast-enhancing tumour which leads to the high local progression rate. Our study aims to identify its progression from the preoperative MR radiomics. 57 newly diagnosed cerebral glioblastoma patients were included. All patients received 5-aminolevulinic acid (5-ALA) fluorescence guidance surgery and postoperative temozolomide concomitant chemoradiotherapy. Preoperative 3 T MRI data including structure MR, perfusion MR, and DTI were obtained. Voxel-based radiomics features extracted from 37 patients were used in the convolutional neural network to train and as internal validation. Another 20 patients of the cohort were tested blindly as external validation. Our results showed that the peritumoural progression areas had higher signal intensity in FLAIR (p = 0.02), rCBV (p = 0.038), and T1C (p = 0.0004), and lower intensity in ADC (p = 0.029) and DTI-p (p = 0.001) compared to non-progression area. The identification of the peritumoural progression area was done by using a supervised convolutional neural network. There was an overall accuracy of 92.6% in the training set and 78.5% in the validation set. Multimodal MR radiomics can demonstrate distinct characteristics in areas of potential progression on preoperative MRI.

Phosphorus spectroscopy in acute TBI demonstrates metabolic changes that relate to outcome in the presence of normal structural MRI.

Metabolic dysfunction is a key pathophysiological process in the acute phase of traumatic brain injury (TBI). Although changes in brain glucose metabolism and extracellular lactate/pyruvate ratio are well known, it was hitherto unknown whether these translate to downstream changes in ATP metabolism and intracellular pH. We have performed the first clinical voxel-based in vivo phosphorus magnetic resonance spectroscopy (31P MRS) in 13 acute-phase major TBI patients versus 10 healthy controls (HCs), at 3T, focusing on eight central 2.5 × 2.5 × 2.5 cm3 voxels per subject. PCr/γATP ratio (a measure of energy status) in TBI patients was significantly higher (median = 1.09) than that of HCs (median = 0.93) (p < 0.0001), due to changes in both PCr and ATP. There was no significant difference in PCr/γATP between TBI patients with favourable and unfavourable outcome. Cerebral intracellular pH of TBI patients was significantly higher (median = 7.04) than that of HCs (median = 7.00) (p = 0.04). Alkalosis was limited to patients with unfavourable outcome (median = 7.07) (p < 0.0001). These changes persisted after excluding voxels with > 5% radiologically visible injury. This is the first clinical demonstration of brain alkalosis and elevated PCr/γATP ratio acutely after major TBI. 31P MRS has potential for non-invasively assessing brain injury in the absence of structural injury, predicting outcome and monitoring therapy response.

Multimodal MRI characteristics of the glioblastoma infiltration beyond contrast enhancement.

Our inability to identify the invasive margin of glioblastomas hampers attempts to achieve local control. Diffusion tensor imaging (DTI) has been implemented clinically to delineate the margin of the tumor infiltration, its derived anisotropic (q) values can extend beyond the contrast-enhanced area and correlates closely with the tumor. However, its correlation with tumor infiltration shown on multivoxel proton magnetic resonance spectroscopy1 (MRS) and perfusion magnetic resonance imaging (MRI) should be investigated. In this study, we aimed to show tissue characteristics of the q-defined peritumoral invasion on MRS and perfusion MRI. Patients with a primary glioblastoma were included (n = 51). Four regions of interest were analyzed; the contrast-enhanced lesion, peritumoral abnormal q region, peritumoral normal q region, and contralateral normal-appearing white matter. MRS, including choline (Cho)/creatinine (Cr), Cho/N-acetyl-aspartate (NAA) and NAA/Cr ratios, and the relative cerebral blood volume (rCBV) were analyzed. Our results showed an increase in the Cho/NAA (p = 0.0346) and Cho/Cr (p = 0.0219) ratios in the peritumoral abnormal q region, suggestive of tumor invasion. The rCBV was marginally elevated (p = 0.0798). Furthermore, the size of the abnormal q regions was correlated with survival; patients with larger abnormal q regions showed better progression-free survival (median 287 versus 53 days, p = 0.001) and overall survival (median 464 versus 274 days, p = 0.006) than those with smaller peritumoral abnormal q regions of interest. These results support how the DTI q abnormal area identifies tumor activity beyond the contrast-enhanced area, especially correlating with MRS.

Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging.

OBJECTIVE: The objective of this study was to characterize the abnormalities revealed by diffusion tensor imaging (DTI) using MR spectroscopy (MRS) and perfusion imaging, and to evaluate the prognostic value of a proposed quantitative measure of tumor invasiveness by combining contrast-enhancing (CE) and DTI abnormalities in patients with glioblastoma. METHODS: Eighty-four patients with glioblastoma were recruited preoperatively. DTI was decomposed into isotropic (p) and anisotropic (q) components. The relative cerebral blood volume (rCBV) was calculated from the dynamic susceptibility contrast imaging. Values of N-acetylaspartate, myoinositol, choline (Cho), lactate (Lac), and glutamate + glutamine (Glx) were measured from multivoxel MRS and normalized as ratios to creatine (Cr). Tumor regions of interest (ROIs) were manually segmented from the CE T1-weighted (CE-ROI) and DTI-q (q-ROI) maps. Perfusion and metabolic characteristics of these ROIs were measured and compared. The relative invasiveness coefficient (RIC) was calculated as a ratio of the characteristic radii of CE-ROI and q-ROI. The prognostic significance of RIC was tested using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: The Cho/Cr, Lac/Cr, and Glx/Cr in q-ROI were significantly higher than CE-ROI (p = 0.004, p = 0.005, and p = 0.007, respectively). CE-ROI had significantly higher rCBV values than q-ROI (p < 0.001). A higher RIC was associated with worse survival in a multivariate overall survival (OS) model (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.06-1.85, p = 0.016) and progression-free survival (PFS) model (HR 1.55, 95% CI 1.16-2.07, p = 0.003). An RIC cutoff value of 0.89 significantly predicted shorter OS (median 384 vs 605 days, p = 0.002) and PFS (median 244 vs 406 days, p = 0.001). CONCLUSIONS: DTI-q abnormalities displayed higher tumor load and hypoxic signatures compared with CE abnormalities, whereas CE regions potentially represented the tumor proliferation edge. Integrating the extents of invasion visualized by DTI-q and CE images into clinical practice may lead to improved treatment efficacy.

Low perfusion compartments in glioblastoma quantified by advanced magnetic resonance imaging and correlated with patient survival.

BACKGROUND AND PURPOSE: Glioblastoma exhibits profound intratumoral heterogeneity in perfusion. Particularly, low perfusion may induce treatment resistance. Thus, imaging approaches that define low perfusion compartments are crucial for clinical management. MATERIALS AND METHODS: A total of 112 newly diagnosed glioblastoma patients were prospectively recruited for maximal safe resection. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from diffusion and perfusion imaging, respectively. Based on the overlapping regions of lowest rCBV quartile (rCBVL) with the lowest ADC quartile (ADCL) and highest ADC quartile (ADCH) in each tumor, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified for volumetric analysis. Lactate and macromolecule/lipid levels were determined from multivoxel MR spectroscopic imaging. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier's and multivariate Cox regression analyses, to evaluate the effects of compartment volume and lactate level on survival. RESULTS: Two compartments displayed higher lactate and macromolecule/lipid levels compared to contralateral normal-appearing white matter (each P < 0.001). The proportion of the ADCL-rCBVL compartment in the contrast-enhancing tumor was associated with a larger infiltration on FLAIR (P < 0.001, rho = 0.42). The minimally invasive phenotype displayed a lower proportion of the ADCL-rCBVL compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005). CONCLUSIONS: Our results suggest that the ADCL-rCBVL compartment may potentially indicate a clinically measurable resistant compartment.

Multi-parametric and multi-regional histogram analysis of MRI: modality integration reveals imaging phenotypes of glioblastoma.

OBJECTIVES: Integrating multiple imaging modalities is crucial for MRI data interpretation. The purpose of this study is to determine whether a previously proposed multi-view approach can effectively integrate the histogram features from multi-parametric MRI and whether the selected features can offer incremental prognostic values over clinical variables. METHODS: Eighty newly-diagnosed glioblastoma patients underwent surgery and chemoradiotherapy. Histogram features of diffusion and perfusion imaging were extracted from contrast-enhancing (CE) and non-enhancing (NE) regions independently. An unsupervised patient clustering was performed by the multi-view approach. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the relevance of patient clustering to survival. The metabolic signatures of patient clusters were compared using multi-voxel spectroscopy analysis. The prognostic values of histogram features were evaluated by survival and ROC curve analyses. RESULTS: Two patient clusters were generated, consisting of 53 and 27 patients respectively. Cluster 2 demonstrated better overall survival (OS) (p = 0.007) and progression-free survival (PFS) (p < 0.001) than Cluster 1. Cluster 2 displayed lower N-acetylaspartate/creatine ratio in NE region (p = 0.040). A higher mean value of anisotropic diffusion in NE region was associated with worse OS (hazard ratio [HR] = 1.40, p = 0.020) and PFS (HR = 1.36, p = 0.031). The seven features selected by this approach showed significantly incremental value in predicting 12-month OS (p = 0.020) and PFS (p = 0.022). CONCLUSIONS: The multi-view clustering method can provide an effective integration of multi-parametric MRI. The histogram features selected may be used as potential prognostic markers. KEY POINTS: • Multi-parametric magnetic resonance imaging captures multi-faceted tumor physiology. • Contrast-enhancing and non-enhancing tumor regions represent different tumor components with distinct clinical relevance. • Multi-view data analysis offers a method which can effectively select and integrate multi-parametric and multi-regional imaging features.