Guiding the first biopsy in glioma patients using estimated Ki-67 maps derived from MRI: conventional versus advanced imaging.

BACKGROUND: Undersampling of gliomas at first biopsy is a major clinical problem, as accurate grading determines all subsequent treatment. We submit a technological solution to reduce the problem of undersampling by estimating a marker of tumor proliferation (Ki-67) using MR imaging data as inputs, against a stereotactic histopathology gold standard. METHODS: MR imaging was performed with anatomic, diffusion, permeability, and perfusion sequences, in untreated glioma patients in a prospective clinical trial. Stereotactic biopsies were harvested from each patient immediately prior to surgical resection. For each biopsy, an imaging description (23 parameters) was developed, and the Ki-67 index was recorded. Machine learning models were built to estimate Ki-67 from imaging inputs, and cross validation was undertaken to determine the error in estimates. The best model was used to generate graphical maps of Ki-67 estimates across the whole brain. RESULTS: Fifty-two image-guided biopsies were collected from 23 evaluable patients. The random forest algorithm best modeled Ki-67 with 4 imaging inputs (T2-weighted, fractional anisotropy, cerebral blood flow, Ktrans). It predicted the Ki-67 expression levels with a root mean square (RMS) error of 3.5% (R2 = 0.75). A less accurate predictive result (RMS error 5.4%, R2 = 0.50) was found using conventional imaging only. CONCLUSION: Ki-67 can be predicted to clinically useful accuracies using clinical imaging data. Advanced imaging (diffusion, perfusion, and permeability) improves predictive accuracy over conventional imaging alone. Ki-67 predictions, displayed as graphical maps, could be used to guide biopsy, resection, and/or radiation in the care of glioma patients.

Glial tumors in brodmann area 6: spread pattern and relationships to motor areas.

The posterior frontal lobe of the brain houses Brodmann area 4, which is the primary motor cortex, and Brodmann area 6, which consists of the supplementary motor area on the medial portion of the hemisphere and the premotor cortex on the lateral portion. In this area, safe resection is dependent on accurate localization of the motor cortex and the central sulcus, which can usually be achieved by using thin-section imaging and confirmed by using other techniques. The most reliable anatomic landmarks are the "hand knob" area and the marginal ramus of the cingulate sulcus. Postoperatively, motor deficits can occur not only because of injury to primary motor cortex but also because of injury to the supplementary motor area. Unlike motor cortex injury, the supplementary motor area syndrome is transient, if it occurs at all. On the lateral hemisphere, motor and language deficits can also occur because of premotor cortex injury, but a dense motor deficit would indicate subcortical injury to the corticospinal tract. The close relationship of the subcortical motor fibers and premotor cortex is illustrated. In contrast to the more constant landmarks of the central sulcus and marginal ramus, which aid in preoperative localization, the variable interruptions in the precentral and cingulate sulci of the posterior frontal lobe seem to provide "cortical bridges" for spread of infiltrating gliomas.

Effects of Radiotherapy in the treatment of multiple myeloma: a retrospective analysis of a Single Institution.

BACKGROUND: Palliative irradiation of osteolytic lesions is a considerable component in the treatment for patients with multiple myeloma. In this study, we analyzed the efficacy of irradiation in these patients. PATIENTS AND METHODS: We retrospectively analyzed 153 patients with multiple myeloma who were admitted to our department between 1989 and 2013. According to the staging system of Durie & Salmon 116 patients were classified as stage III. 107/153 patients were treated with radiotherapy of at least one and up to 6 bony lesions at different times. In order to evaluate the effect of local radiotherapy on pain relief and bone recalcification a uni- and multivariate analysis was performed using a binary logistic regression model to correct for multiple measurements. Complete information on dose, fractionation and volume of radiotherapy was available from 81 patients treated in 136 target volumes for pain relief, and from 69 patients treated in 108 target volumes for recalcification. Total radiation doses varied between 8 Gy to 50 Gy (median dose 25 Gy in 2.5 Gy fractions, 5 times a week). RESULTS: Radiotherapy resulted in complete local pain relief in 31% and partial local pain relief in 54% of the patients. In the univariate analysis, higher total radiation doses (p = 0.023) and higher age (p = 0.014) at the time of radiotherapy were significantly associated with a higher likelihood of pain relief, whereas no significant association was detected for concurrent systemic treatment, type and stage of myeloma and location of bone lesions. The same variables were independent predictors for pain relief in the multivariate analysis. Recalcification was observed in 48% of irradiated bone lesions. In the uni- and multivariate analysis higher radiation doses were significantly associated (p = 0.048) with an increased likelihood of recalcification. Side effects of radiotherapy were generally mild. CONCLUSIONS: Higher total biological radiation doses were associated with better pain relief and recalcification in this retrospective evaluation of multiple myeloma patients. In addition, in the elderly the therapeutic measures appear to develop a better analgesic effect.

Synchronous rosette-forming glioneuronal tumor and diffuse astrocytoma with molecular characterization: a case report.

Rosette-forming glioneuronal tumor (WHO grade I) is a rare neoplasm primarily arising in young adults that is characterized by distinctive neurocytic rosette formation, a spindled glial component resembling pilocytic astrocytoma, and a high incidence of PIK3CA mutation. Low-grade diffuse astrocytoma (WHO grade II), on the other hand, is far more common and is characterized by a high incidence of IDH mutation. Here we report a patient with simultaneous presentation of a midbrain-cerebellar rosetteforming glioneuronal tumor and a cerebral diffuse astrocytoma. Molecular characterization of both tumors confirmed characteristic, mutually exclusive, distinct signatures, with the rosette-forming glioneuronal tumor exhibiting a previously unreported novel PIK3CA gene mutation.

CT findings in temporal bone osteoradionecrosis.

PURPOSE: The goal of this study was to describe computed tomographic findings in patients with clinically proven temporal bone (TB) osteoradionecrosis (ORN) (TB-ORN). MATERIALS AND METHODS: Computed tomographic scans of 20 patients were retrospectively evaluated for bony and soft tissue abnormalities. Clinical severity was graded based on level of therapy administered: mild (observation), moderate (antibiotics/hyperbaric oxygen), or severe (surgery). RESULTS: Radiation dose to the primary tumor ranged from 30 to 75.6 Gy. Time to onset of ORN from completion of radiation therapy was 2 to 22 years (median, 7 years). CLINICAL FINDINGS: exposed bone, 20 of the 20 patients; otorrhea, 17 of the 20 patients; hearing loss, 11 of the 20 patients; otalgia, 10 of the 20 patients; facial nerve paralysis, 2 of the 20 patients; gait imbalance, 2 of the 20 patients. Computed tomographic findings: external auditory canal erosions, 18 of the 20 patients; mastoid effusion, 18 of the 20 patients; mastoid bony coalescence, 5 of the 20 patients; enhancing soft tissue, 6 of the 20 patients; soft tissue gas, 6 of the 20 patients; temporomandibular joint/condylar erosion, 3 of the 20 patients.Three patients developed an abscess. CONCLUSION: Mastoid effusion and external auditory canal erosions are commonly seen with TB-ORN. Clinically moderate or severe cases of TB-ORN are more likely to demonstrate enhancing soft tissue (P = 0.002), soft tissue gas (P = 0.002), and temporomandibular joint involvement (P = 0.07).

Change in postsurgical cavity size within the first 30 days correlates with extent of surrounding edema: consequences for postoperative radiosurgery.

OBJECTIVE: Resection cavity diameter of less than 40 mm is required to be eligible for stereotactic radiosurgery (SRS), after gross total resection of brain metastasis at our institution. Our study evaluates the correlation between vasogenic edema and change in cavity size for 30 days. METHODS: Cavity size was measured on the postoperative and follow-up magnetic resonance imaging. Vasogenic edema was quantified as the largest axial measurement of T2 hyperintensity surrounding the resection cavity (postoperative magnetic resonance imaging). RESULTS: Thirty-nine resection cavities (37 patients) were reviewed. There was a statistically significant (Pearson coefficient = -0.35; P = 0.02) negative correlation between edema and change in cavity size. An arbitrary cutoff value of a 15-mm edema yielded a sensitivity of 96% and a specificity of 65% (P < 0.001) to predict 10% decrease in cavity size. CONCLUSIONS: In patients with cavity size close to the size cutoff for SRS, rescanning closer to the date of SRS should be considered, especially if there is significant edema surrounding the cavity.

Increased CD44s and decreased CD44v6 RNA expression are associated with better survival in myxofibrosarcoma patients: a pilot study.

BACKGROUND: New prognostic markers may be of value in determining survival and informing decisions of adjuvant treatment in the heterogeneous group of soft tissue sarcomas known as malignant fibrous sarcomas (MFS). Increased CD44 expression has been associated with a better outcome in cancers such as bladder tumors and could potentially relate to cell-cell interaction as a marker for potential invasion/metastasis. The aim of this pilot study was to determine if there is a correlation between the expression rate of CD44 in adult patients with MFS and clinical outcomes. METHODS: The clinical outcome of 34 adult MFS patients (19 males and 15 females, average age 62 years, median 63 years, range: 38-88 years) who underwent surgical treatment were evaluated. Twenty-five of these patients had additional adjuvant radiotherapy. Extracted RNA from sarcoma tissues was used to measure the transcripts of CD44s (standard form) and isoform expression.The pooled data for each variant of CD44 was divided in half at the median expression value into two equally sized groups (low and high). Survival modeling and multivariate analysis were used with these two groups to determine if there were differences in survival times and whether this was independent of known factors such as tumor stage/grade, patient age and resection margin status. RESULTS: High CD44s and low of CD44v6 expression significantly correlated with an improved outcome (P <0.05 and P <0.02, respectively) whereas CD44v8 and hCD44 (isoforms) did not. Differences in survival were apparent within 6-12 months of operation with >30% difference in survival between low/high expressions at 5 years. These finding were independent of the other measured MFS survival predictors, though the group was homogenous. CONCLUSIONS: High CD44s and low CD44v6 expression may be an independent predictor of improved survival in MFS patients in this pilot data. This is contrary to other MFS data, which did not account for the CD44 isoforms but is confirmed by data from other cancer types. Further investigation is needed to confirm CD44 isoform expression data as a relevant survival biomarker and whether it could be used to inform clinical decisions such as adjuvant therapy.

Preliminary experience with diffusion tensor imaging before and after re-irradiation treatments in children with progressive diffuse pontine glioma.

PURPOSE: The purpose of this study is to evaluate quantitative changes in diffusion tensor imaging (DTI) tractography and fractional anisotropy (FA) of the pons along with clinical correlation, in patients who receive re-irradiation for progressive diffuse intrinsic pontine glioma (DIPG). METHODS: A retrospective case review of children with progressive DIPG who received re-irradiation at our institution from 2007 to 2011 after approval from the Institutional Review Board was performed. Tractography analysis and FA were analyzed pre and post-re-irradiation, and correlation with clinical features and MR imaging was performed. RESULTS: DTI analysis showed reduced values of FA on tumor progression. Increase in the FA values was noted after re-irradiation in these patients. This correlated with clinical improvement. These changes were concordant with the 3D tractography analysis which showed better visualization of the corticospinal tracts as they course through brainstem and posterior transverse pontine fibers following re-irradiation. CONCLUSION: Serial changes in the FA values using DTI could provide clinically more correlative information in patients with progressive DIPG, who receive re-irradiation. Though the use and results of this modality has been reported in the newly diagnosed DIPG before, evaluation of DTI in children who receive re-irradiation for progressive DIPG has not been reported earlier. Though limited by the small sample size and treatment variability, this study for the first time shows the preliminary experience, potential, and likely efficacy of complementing DTI analysis to routine neuroimaging also in patients re-irradiated for progressive DIPG to better assess treatment response.

Real-time atlas-based stereotactic neuronavigation.

BACKGROUND: Surgery for tumors in eloquent brain faces immense challenges when attempting to maximize resection and avoid neurological deficits. OBJECTIVE: In order to give the surgeon real-time atlas-based anatomic information linked to the patient's anatomy, we developed a software-based interface between deformable anatomic templates (DATs) and an intraoperative navigation system. METHODS: Magnetic resonance imaging (MRI), diffusion tensor imaging, and/or functional MRI were performed on 3 patients preoperatively for the purposes of tumor resection by the use of neuronavigation. The DAT was registered to the patients' navigation coordinate system and utilized coordinates from the navigation system during surgery. This provided the surgeon with a list of proximal anatomic and functional structures and a real-time image of the atlas at that location fused to the patient's MRI. The clinical feasibility of this approach was evaluated during the resection of 3 eloquent tumors (right postcentral gyrus, left inferior frontal gyrus, and left occipital cuneus gyrus). RESULTS: Tumor resection was performed successfully in all 3 patients. With the use of the coordinates from the navigation system, anatomic and functional structures and their distances were visualized interactively during tumor resection by using the DAT. CONCLUSION: This is a proof of concept that an interactive atlas-based navigation can provide detailed anatomic and functional information that supplements MRI, diffusion tensor imaging, and functional MRI. The atlas-based navigation generated distances to important anatomic structures from the navigation probe tip. It can be used to guide direct electrical stimulation and highlight areas to avoid during tumor resection. ABBREVIATIONS: DAT, deformable anatomic templateDES, direct electrical stimulationDTI, diffusion tensor imagingfMRI, functional magnetic resonance imaging.

Severe everolimus-induced steatohepatis: a case report.

The mammalian target of rapamycin inhibitors are normally favored as immunosuppressant agents for solid organ transplantation such as kidney, liver or heart. Only in recent years have they been increasingly administered for the treatment of neuroendocrine tumors. Even though mammalian target of rapamycin inhibitors are known to exhibit specific side effects, everolimus-related severe hepatic steatosis has not as yet been described in the literature. We report the case of a 76-year-old man who developed severe hepatic steatosis within four weeks of treatment with everolimus as concomitant tumor therapy for a progressively growing neuroendocrine carcinoma of the ileum. A diagnosis of hepatic steatosis was established using computer tomography and fibroscan©. Other underlying causes for steatosis hepatis could be excluded. Further studies are warranted to explain the underlying mechanisms.

Deformable anatomic templates improve analysis of gliomas with minimal mass effect in eloquent areas.

BACKGROUND: Despite improvements in advanced magnetic resonance imaging and intraoperative mapping, cases remain in which it is difficult to determine whether viable eloquent structures are involved by a glioma. A novel software program, deformable anatomic templates (DAT), rapidly embeds the normal location of eloquent cortex and functional tracts in the magnetic resonance images of glioma-bearing brain. OBJECTIVE: To investigate the feasibility of the DAT technique in patients with gliomas related to eloquent brain. METHODS: Forty cases of gliomas (grade II-IV) with minimal mass effect were referred for a prospective preoperative and postoperative DAT analysis. The DAT results were compared with the patient's functional magnetic resonance imaging, diffusion tensor imaging, operative stimulation, and new postoperative clinical deficits. RESULTS: Fifteen of the 40 glioma patients had overlap between tumor and eloquent structures. Immediate postoperative neurological deficits were seen in 9 cases in which the DAT showed the eloquent area both within the tumor and within or at the edge of the resection cavity. In 6 cases with no deficits, DAT placed the eloquent area in the tumor but outside the resection cavity. CONCLUSION: This is proof of concept that DAT can improve the analysis of diffuse gliomas of any grade by efficiently alerting the surgeon to the possibility of eloquent area invasion. The technique is especially helpful in diffuse glioma because these tumors tend to infiltrate rather than displace eloquent structures. DAT is limited by tract displacement in gliomas that produces moderate to severe mass effect.

Residual nodal disease in patients with advanced-stage oropharyngeal squamous cell carcinoma treated with definitive radiation therapy and posttreatment neck dissection: Association with locoregional recurrence, distant metastasis, and decreased survival.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in frequency. We reviewed patients with advanced-stage OPSCC treated with chemoradiation to assess the impact of residual neck disease on survival. METHODS: We reviewed 202 patients with OPSCC between 1990 and 2010 treated with primary chemoradiation followed by neck dissection. Imaging was analyzed using RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria. Survival was evaluated using both univariate and multivariate analyses. RESULTS: Overall survival at 5 years was 89%. Forty-two patients (21%) had residual disease in the neck (pN+). pN+ was associated with greater locoregional recurrence (LRR) and distant metastasis (DM) and decreased survival. No clinicopathologic factors were predictive of pN+. Contrasted posttreatment CT had low sensitivity and specificity. CONCLUSIONS: In advanced OPSCC pN+, patients have higher rates of LRR and DM. Neither clinicopathologic factors nor posttreatment imaging was predictive of pN+, although increased use of modern imaging may reduce the rate of negative neck dissections.

Superimposed infection in mandibular osteoradionecrosis: diagnosis and outcomes.

BACKGROUND: Radiation therapy can result in osteoradionecrosis (ORN) and mucosal ulceration predisposing to infection. METHODS: Fourteen patients presenting with infectious sequelae related to mandibular ORN were retrospectively reviewed. RESULTS: In most patients, infection followed diagnosis of ORN; but in 4 patients, ORN was not diagnosed until after the time of infection and imaging. An early imaging finding of ORN was lingual cortical defects near the last molar. Pain followed by erythema, purulent drainage, and subperiosteal abscess by imaging were the most common signs of infection. In most patients, conservative management eventually failed and segmental mandibulectomies were required. CONCLUSIONS: Soft tissue infection with characteristic bone findings such as subperiosteal abscess and cortical bone erosions helps to distinguish infected ORN from recurrent tumor or sterile ORN. In patients previously treated with radiation who present with infection, pain or an avid PET scan with bone involvement, the mandible should be scrutinized.

Deformable anatomic templates embed knowledge into patient's brain images: Part 1. Construction and display.

OBJECTIVE: This paper describes the methods used to create annotated deformable anatomic templates (DATs) and display them in a patient's axial 2-dimensional and reformatted volume brain images. METHODS: A senior neuroradiologist annotated and manually segmented 1185 color-coded structures on axial magnetic resonance images of a normal template brain using domain knowledge from multiple medical specialties. Besides the visible structures, detailed pathways for vision, speech, cognition, and movement were charted. This was done by systematically joining visible anatomic anchor points and selecting the best fit based on comparisons with cadaver dissections and the constraints defined on the companion 2-dimensional images. RESULTS: The DAT is commercially available for use on a picture archiving and communication system or as a standalone workstation. CONCLUSIONS: The DAT can quickly embed extensive, clinically useful functional neuroanatomic knowledge into the patient's brain images. Besides labeling visible structures, DAT displays clinically important, previously uncharted subdivisions of the fiber tracts.

Deformable anatomic templates embed knowledge into brain images: part 2. Validation using functional magnetic resonance imaging of the motor hand.

OBJECTIVE: This study evaluated the concordance between the Deformable Anatomic Template (DAT)-identified origin of motor hand fibers and localization of the motor cortex of the hand by functional magnetic resonance imaging (fMRI). METHODS: Preoperative fMRI during hand motor tasks was performed on 36 hemispheres in 26 patients with gliomas in or near eloquent areas. Reformatted volume-rendered surface images were labeled with the DAT's hand motor fibers and fMRI data. Five reviewers assessed the data for concordance. RESULTS: Available fMRI data were diagnostically usable in 92% (33/36 analyzed hemispheres), with DAT anatomic accuracy in the remaining cases. The DAT prediction and fMRI findings were concordant in all 9 normal hemispheres and in 20 (83%) of 24 glioma-bearing hemispheres. The 4 discordant cases resulted from substantial mass effect by large frontal tumors. CONCLUSIONS: This study validated DAT's anatomic atlas and alignment process for the expected position of the motor cortex of the hand.

Multidetector CT evaluation of active extravasation in blunt abdominal and pelvic trauma patients.

Timely localization of a bleeding source can improve the efficacy of trauma management, and improvements in the technology of computed tomography (CT) have expedited the work-up of the traumatized patient. The classic pattern of active extravasation (ie, administered contrast agent that has escaped from injured arteries, veins, or urinary tract) at dual phase CT is a jet or focal area of hyperattenuation within a hematoma that fades into an enlarged, enhanced hematoma on delayed images. This finding indicates significant bleeding and must be quickly communicated to the clinician, since potentially lifesaving surgical or endovascular repair may be necessary. Active extravasation can be associated with other injuries to arteries, such as a hematoma or a pseudoaneurysm. Both active extravasation and pseudoaneurysm (unlike bone fragments and dense foreign bodies) change in appearance on delayed images, compared with their characteristics on arterial images. Other clues to the location of vessel injury include lack of vascular enhancement (caused by occlusion or spasm), vessel irregularity, size change (such as occurs with pseudoaneurysm), and an intimal flap (which signifies dissection). The sentinel clot sign is an important clue for locating the bleeding source when other more localizing findings of vessel injury are not present. Timely diagnosis, differentiation of vascular injuries from other findings of trauma, signs of depleted intravascular volume, and localization of vascular injury are important to convey to interventional radiologists or surgeons to improve trauma management.