Utility of Zero-Echo time sequence as an adjunct for MR evaluation of degenerative disease in the cervical spine.

OBJECTIVE: Determine the utility of ZTE as an adjunct to routine MR for assessing degenerative disease in the cervical spine. METHODS: Retrospective study on 42 patients with cervical MR performed with ZTE from 1/1/2022 to 4/30/22. Fellowship trained radiologists evaluated each cervical disc level for neural foraminal (NF) narrowing, canal stenosis (CS), facet arthritis (FA), and presence of ossification of the posterior longitudinal ligament (OPLL). When NF narrowing and CS were present, the relative contributions of bone and soft disc were determined and a confidence level for doing so was assigned. Comparisons were made between assessments on routine MR without and with ZTE. RESULTS: With ZTE added, bone contribution as a cause of NF narrowing increased in 47% (n = 110) of neural foramina and decreased in 12% (n = 29) (p = < 0.001). Bone contribution as a cause of CS increased in 25% (n = 33) of disc levels and decreased in 10% (n = 13) (p = 0.013). Confidence increased in identifying the cause of NF narrowing (p = < 0.001)) and CS (p = 0.009) with ZTE. The cause of NF narrowing (p = 0.007) and CS (p = 0.041) changed more frequently after ZTE was added when initial confidence in making the determination was low. There was no change in detection of FA or presence of OPLL with ZTE. CONCLUSION: Addition of ZTE to a routine cervical spine MR changes the assessment of the degree of bone involvement in degenerative cervical spine pathology.

Tailored magnetic resonance fingerprinting.

Neuroimaging of certain pathologies requires both multi-parametric qualitative and quantitative imaging. The role of the quantitative MRI (qMRI) is well accepted but suffers from long acquisition times leading to patient discomfort, especially in geriatric and pediatric patients. Previous studies show that synthetic MRI can be used in order to reduce the scan time and provide qMRI as well as multi-contrast data. However, this approach suffers from artifacts such as partial volume and flow. In order to increase the scan efficiency (the number of contrasts and quantitative maps acquired per unit time), we designed, simulated, and demonstrated rapid, simultaneous, multi-contrast qualitative (T1 weighted, T1 fluid attenuated inversion recovery (FLAIR), T2 weighted, water, and fat), and quantitative imaging (T1 and T2 maps) through the approach of tailored MR fingerprinting (TMRF) to cover whole-brain in approximately four minutes. We performed TMRF on in vivo four healthy human brains and in vitro ISMRM/NIST phantom and compared with vendor supplied gold standard (GS) and MRF sequences. All scans were performed on a 3 T GE Premier system and images were reconstructed offline using MATLAB. The reconstructed qualitative images were then subjected to custom DL denoising and gradient anisotropic diffusion denoising. The quantitative tissue parametric maps were reconstructed using a dense neural network to gain computational speed compared to dictionary matching. The grey matter and white matter tissues in qualitative and quantitative data for the in vivo datasets were segmented semi-automatically. The SNR and mean contrasts were plotted and compared across all three methods. The GS images show better SNR in all four subjects compared to MRF and TMRF (GS > TMRF>MRF). The T1 and T2 values of MRF are relatively overestimated as compared to GS and TMRF. The scan efficiency for TMRF is 1.72 min-1 which is higher compared to GS (0.32 min-1) and MRF (0.90 min-1).

Association of Absent or Trace Fluid in the Maxillary Sinus and Inferior Rectus Muscle Entrapment in Patients With Orbital Floor Fracture.

Inferior rectus (IR) entrapment requires urgent surgical intervention in patients with traumatic orbital floor fracture (OFF). We evaluated 47 patients who underwent CT showing acute OFF, 10 of whom had surgically confirmed entrapment. Absent or trace dependent fluid in the ipsilateral maxillary sinus had sensitivity of 40% and specificity of 95% for entrapment. In comparison, sensitivity and specificity were 80% and 78% for IR thickening and 70% and 59% for sinus herniation of orbital contents.

Chronic convection-enhanced delivery of topotecan for patients with recurrent glioblastoma: a first-in-patient, single-centre, single-arm, phase 1b trial.

BACKGROUND: Topotecan is cytotoxic to glioma cells but is clinically ineffective because of drug delivery limitations. Systemic delivery is limited by toxicity and insufficient brain penetrance, and, to date, convection-enhanced delivery (CED) has been restricted to a single treatment of restricted duration. To address this problem, we engineered a subcutaneously implanted catheter-pump system capable of repeated, chronic (prolonged, pulsatile) CED of topotecan into the brain and tested its safety and biological effects in patients with recurrent glioblastoma. METHODS: We did a single-centre, open-label, single-arm, phase 1b clinical trial at Columbia University Irving Medical Center (New York, NY, USA). Eligible patients were at least 18 years of age with solitary, histologically confirmed recurrent glioblastoma showing radiographic progression after surgery, radiotherapy, and chemotherapy, and a Karnofsky Performance Status of at least 70. Five patients had catheters stereotactically implanted into the glioma-infiltrated peritumoural brain and connected to subcutaneously implanted pumps that infused 146 µM topotecan 200 µL/h for 48 h, followed by a 5-7-day washout period before the next infusion, with four total infusions. After the fourth infusion, the pump was removed and the tumour was resected. The primary endpoint of the study was safety of the treatment regimen as defined by presence of serious adverse events. Analyses were done in all treated patients. The trial is closed, and is registered with ClinicalTrials.gov, NCT03154996. FINDINGS: Between Jan 22, 2018, and July 8, 2019, chronic CED of topotecan was successfully completed safely in all five patients, and was well tolerated without substantial complications. The only grade 3 adverse event related to treatment was intraoperative supplemental motor area syndrome (one [20%] of five patients in the treatment group), and there were no grade 4 adverse events. Other serious adverse events were related to surgical resection and not the study treatment. Median follow-up was 12 months (IQR 10-17) from pump explant. Post-treatment tissue analysis showed that topotecan significantly reduced proliferating tumour cells in all five patients. INTERPRETATION: In this small patient cohort, we showed that chronic CED of topotecan is a potentially safe and active therapy for recurrent glioblastoma. Our analysis provided a unique tissue-based assessment of treatment response without the need for large patient numbers. This novel delivery of topotecan overcomes limitations in delivery and treatment response assessment for patients with glioblastoma and could be applicable for other anti-glioma drugs or other CNS diseases. Further studies are warranted to determine the effect of this drug delivery approach on clinical outcomes. FUNDING: US National Institutes of Health, The William Rhodes and Louise Tilzer Rhodes Center for Glioblastoma, the Michael Weiner Glioblastoma Research Into Treatment Fund, the Gary and Yael Fegel Foundation, and The Khatib Foundation.

The impact of the COVID-19 pandemic on neuroimaging volume in New York City.

BACKGROUND AND PURPOSE: The COVID-19 pandemic acutely disrupted all facets of healthcare, with future implications that are expected to resonate for many years. We investigated the effect of the pandemic on neuroimaging volume, hypothesizing that all representative studies would experience a reduction in volume, with those typically performed in the inpatient setting (noncontrast enhanced CT head and CTA head/neck) taking longer to recover to pre-pandemic volumes compared to studies typically performed in the outpatient setting (MR brain with and without and MR lumbar spine without). MATERIALS AND METHODS: We retrospectively queried our institution's radiology reporting system to collect weekly data for 1 year following the World Health Organization declaration of a pandemic (11 March 2020-9 March 2021) and compared them to imaging volumes from the previous year (11 March 2019-9 March 2020). We subsequently analyzed quarterly data (e.g., first quarter comparison: 3/11/2020-6/9/2020 was compared to 3/11/2019-6/9/2019). RESULTS: All studies experienced decreased volume during the first quarter of the year following onset of the COVID-19 pandemic, with noncontrast enhanced CT head failing to recover to pre-pandemic volumes. CTA head/neck actually surpassed pre-pandemic volume by the second quarter of the year. MRI brain w/wo and MRI lumbar spine without recovered to baseline volume by the second quarter. CONCLUSION: Noncontrast enhanced CT head did not recover pre-pandemic imaging volume. CTA head/neck volume initially decreased, however volume increased above pre-pandemic levels during the second quarter; this finding may be attributable to a prothrombotic state in COVID-19 patients.

Brain Magnetic Resonance Imaging and Angiography in Children with Sickle Cell Anaemia in Uganda in a Cross-Sectional Sample.

OBJECTIVE: Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injury. We performed brain magnetic resonance imaging and angiography (MRI-MRA) in Ugandan children with SCA to identify structural cerebrovascular abnormalities and examine their relationship to standardized clinical assessments. METHODS: A sub-sample (n=81) was selected from a cross-sectional study of children attending SCA clinic, including 52 (64.2%) with and 29 (35.8%) without clinically detected abnormalities. Clinical evaluation included assessment for prior stroke, cognitive testing and cerebral arterial transcranial doppler (TCD) flow velocity. MRI-MRA scans were interpreted by at least two neuroradiologists. RESULTS: Mean age was 6.5±2.7 years, with 39 (48.1%) female. Mean haemoglobin was 7.3±0.9 g/dl. Overall, 13 (16.0%) were malnourished. Infarcts and/or stenoses were detected in 55 (67.9%) participants, with stenoses primarily in the anterior circulation. Infarcts were seen in those with normal 17/29 (58.6%) or abnormal 34/52 (65.4%) clinical testing (p=0.181). Neither abnormal MRI nor MRA was associated with age, sex, haemoglobin, or malnutrition. Abnormal MRA was highly associated with infarcts (p<0.0001). Participants with abnormal imaging had two-fold higher proportion of stroke on exam and/or impaired cognition. Stroke on exam was strongly associated with an imaging abnormality after adjusting for age, sex, malnutrition, and haemoglobin (OR 11.8, 95%CI 1.87-74.2). CONCLUSION: Over half of these SCA children had cerebrovascular infarcts and/or arterial stenoses. Cerebrovascular disease was frequently undetectable by clinical assessments. While rarely available in under-resourced settings, MRI-MRA brain imaging is an important tool for defining SCA cerebrovascular disease and for assessing impact of clinical intervention trials.

Neuronophagia and microglial nodules in a SARS-CoV-2 patient with cerebellar hemorrhage.

We document the neuropathologic findings of a 73-year old man who died from acute cerebellar hemorrhage in the context of relatively mild SARS-CoV2 infection. The patient developed sudden onset of headache, nausea, and vomiting, immediately followed by loss of consciousness on the day of admission. Emergency medical services found him severely hypoxemic at home, and the patient suffered a cardiac arrest during transport to the emergency department. The emergency team achieved return of spontaneous circulation after over 17 min of resuscitation. A chest radiograph revealed hazy bilateral opacities; and real-time-PCR for SARS-CoV-2 on the nasopharyngeal swab was positive. Computed tomography of the head showed a large right cerebellar hemorrhage, with tonsillar herniation and intraventricular hemorrhage. One day after presentation, he was transitioned to comfort care and died shortly after palliative extubation. Autopsy performed 3 h after death showed cerebellar hemorrhage and acute infarcts in the dorsal pons and medulla. Remarkably, there were microglial nodules and neuronophagia bilaterally in the inferior olives and multifocally in the cerebellar dentate nuclei. This constellation of findings has not been reported thus far in the context of SARS-CoV-2 infection.

Fully Automated Segmentation Algorithm for Perihematomal Edema Volumetry After Spontaneous Intracerebral Hemorrhage.

Background and Purpose- Perihematomal edema (PHE) is a promising surrogate marker of secondary brain injury in patients with spontaneous intracerebral hemorrhage, but it can be challenging to accurately and rapidly quantify. The aims of this study are to derive and internally validate a fully automated segmentation algorithm for volumetric analysis of PHE. Methods- Inpatient computed tomography scans of 400 consecutive adults with spontaneous, supratentorial intracerebral hemorrhage enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) were separated into training (n=360) and test (n=40) datasets. A fully automated segmentation algorithm was derived from manual segmentations in the training dataset using convolutional neural networks, and its performance was compared with that of manual and semiautomated segmentation methods in the test dataset. Results- The mean volumetric dice similarity coefficients for the fully automated segmentation algorithm were 0.838±0.294 and 0.843±0.293 with manual and semiautomated segmentation methods as reference standards, respectively. PHE volumes derived from the fully automated versus manual (r=0.959; P<0.0001), fully automated versus semiautomated (r=0.960; P<0.0001), and semiautomated versus manual (r=0.961; P<0.0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 18.0±1.8 seconds/scan) quantified PHE volumes at a significantly faster rate than both of the manual (mean 316.4±168.8 seconds/scan; P<0.0001) and semiautomated (mean 480.5±295.3 seconds/scan; P<0.0001) segmentation methods. Conclusions- The fully automated segmentation algorithm accurately quantified PHE volumes from computed tomography scans of supratentorial intracerebral hemorrhage patients with high fidelity and greater efficiency compared with manual and semiautomated segmentation methods. External validation of fully automated segmentation for assessment of PHE is warranted.

Fully Automated Segmentation Algorithm for Hematoma Volumetric Analysis in Spontaneous Intracerebral Hemorrhage.

Background and Purpose- Hematoma volume measurements influence prognosis and treatment decisions in patients with spontaneous intracerebral hemorrhage (ICH). The aims of this study are to derive and validate a fully automated segmentation algorithm for ICH volumetric analysis using deep learning methods. Methods- In-patient computed tomography scans of 300 consecutive adults (age ≥18 years) with spontaneous, supratentorial ICH who were enrolled in the ICHOP (Intracerebral Hemorrhage Outcomes Project; 2009-2018) were separated into training (n=260) and test (n=40) datasets. A fully automated segmentation algorithm was derived using convolutional neural networks, and it was trained on manual segmentations from the training dataset. The algorithm's performance was assessed against manual and semiautomated segmentation methods in the test dataset. Results- The mean volumetric Dice similarity coefficients for the fully automated segmentation algorithm when tested against manual and semiautomated segmentation methods were 0.894±0.264 and 0.905±0.254, respectively. ICH volumes derived from fully automated versus manual (R2=0.981; P<0.0001), fully automated versus semiautomated (R2=0.978; P<0.0001), and semiautomated versus manual (R2=0.990; P<0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 12.0±2.7 s/scan) was significantly faster than both of the manual (mean 201.5±92.2 s/scan; P<0.001) and semiautomated (mean 288.58±160.3 s/scan; P<0.001) segmentation methods. Conclusions- The fully automated segmentation algorithm quantified hematoma volumes from computed tomography scans of supratentorial ICH patients with similar accuracy and substantially greater efficiency compared with manual and semiautomated segmentation methods. External validation of the fully automated segmentation algorithm is warranted.

Extent of BOLD Vascular Dysregulation Is Greater in Diffuse Gliomas without Isocitrate Dehydrogenase 1 R132H Mutation.

Purpose To determine the effect that R132H mutation status of diffuse glioma has on extent of vascular dysregulation and extent of residual blood oxygen level-dependent (BOLD) abnormality after surgical resection. Materials and Methods This study was an institutional review board-approved retrospective analysis of an institutional database of patients, and informed consent was waived. From 2010 to 2017, 39 treatment-naïve patients with diffuse glioma underwent preoperative echo-planar imaging and BOLD functional magnetic resonance imaging. BOLD vascular dysregulation maps were made by identifying voxels with time series similar to tumor and dissimilar to healthy brain. The spatial overlap between tumor and vascular dysregulation was characterized by using the Dice coefficient, and areas of BOLD abnormality outside the tumor margins were quantified as BOLD-only fraction (BOF). Linear regression was used to assess effects of R132H status on the Dice coefficient, BOF, and residual BOLD abnormality after surgical resection. Results When compared with R132H wild-type (R132H-) gliomas, R132H-mutated (R132H+) gliomas showed greater spatial overlap between BOLD abnormality and tumor (mean Dice coefficient, 0.659 ± 0.02 [standard error] for R132H+ and 0.327 ± 0.04 for R132H-; P < .001), less BOLD abnormality beyond the tumor margin (mean BOF, 0.255 ± 0.03 for R132H+ and 0.728 ± 0.04 for R132H-; P < .001), and less postoperative BOLD abnormality (residual fraction, 0.046 ± 0.0047 for R132H+ and 0.397 ± 0.045 for R132H-; P < .001). Receiver operating characteristic curve analysis showed high sensitivity and specificity in the discrimination of R132H+ tumors from R132H- tumors with calculation of both Dice coefficient and BOF (area under the receiver operating characteristic curve, 0.967 and 0.977, respectively). Conclusion R132H mutation status is an important variable affecting the extent of tumor-associated vascular dysregulation and the residual vascular dysregulation after surgical resection. © RSNA, 2018 Online supplemental material is available for this article.

Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation.

Progressive neurovasculopathy in children with sickle cell disease (SCD) results in decreased cognitive function and quality of life (QoL). Hematopoietic cell transplantation (HCT) is believed to halt progression of neurovasculopathy. Quantitative analysis of T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) for white matter hyperintensity (WMH) burden provides a meaningful estimate of small vessel cerebrovascular disease. We asked if quantitative analysis of WMH could complement standardized clinical assessment of MRI/magnetic resonance angiography (MRA) for assessing SCD central nervous system vasculopathy before and after HCT. Retrospective longitudinal clinical examination of scheduled annual MRI/MRA and quantitative analysis of WMH were performed before and 1 to 7 years after HCT at scheduled annual intervals, along with QoL measurements, in children who had engrafted after HCT. Of 18 patients alive and persistently engrafted (median age, 9.1 years), pretransplantation MRI demonstrated that 9 and 5 had sickle-related stroke and/or small infarcts, respectively. Patients were divided into WMH severity tertiles based on pretransplantation WMH volumes. MRI and WMH were assessed 1 to 7 years after HCT. MRI/MRA and WMH volume were stable or slightly better in 17 of 18 patients. By parent- and self-report, post-HCT QoL improved for children in the lowest WMH tertile significantly more than in the other groups. Based on this single-institution retrospective sample, we report that WMH appears to quantitatively support MRI-based findings that HCT stabilizes long-term small and large vessel cerebrovascular changes and is associated with the degree of improved QoL. While confirmation in larger prospective studies and evaluation by neurocognitive testing are needed, these findings suggest that WMH is a useful biomarker of neurovasculopathy after transplantation for SCD.

Predicting Glioblastoma Recurrence by Early Changes in the Apparent Diffusion Coefficient Value and Signal Intensity on FLAIR Images.

OBJECTIVE: Recurrence of glioblastoma multiforme (GBM) arises from areas of microscopic tumor infiltration that have yet to disrupt the blood-brain barrier. We hypothesize that these microscopic foci of invasion cause subtle variations in the apparent diffusion coefficient (ADC) and FLAIR signal detectable with the use of computational big-data modeling. MATERIALS AND METHODS: Twenty-six patients with native GBM were studied immediately after undergoing gross total tumor resection. Within the peritumoral region, areas of future GBM recurrence were identified through coregistration of follow-up MRI examinations. The likelihood of tumor recurrence at each individual voxel was assessed as a function of signal intensity on ADC maps and FLAIR images. Both single and combined multivariable logistic regression models were created. RESULTS: A total of 419,473 voxels of data (105,477 voxels of data within tumor recurrence and 313,996 voxels of data on surrounding peritumoral edema) were analyzed. For future areas of recurrence, a 9.5% decrease in the ADC value (p < 0.001) and a 9.2% decrease in signal intensity on FLAIR images (p < 0.001) were shown, compared with findings for the surrounding peritumoral edema. Logistic regression revealed that the amount of signal loss on both ADC maps and FLAIR images correlated with the likelihood of tumor recurrence. A combined multiparametric logistic regression model was more specific in the prediction of tumor recurrence than was either single-variable model alone. CONCLUSION: Areas of future GBM recurrence exhibit small but highly statistically significant differences in signal intensity on ADC maps and FLAIR images months before the development of abnormal enhancement occurs. A multiparametric logistic model calibrated to these changes can be used to estimate the burden of microscopic nonenhancing tumor and predict the location of recurrent disease. Computational big-data modeling performed at the voxel level is a powerful technique capable of discovering important but subtle patterns in imaging data.

Glioblastoma Induces Vascular Dysregulation in Nonenhancing Peritumoral Regions in Humans.

OBJECTIVE: Glioblastoma is an invasive primary brain malignancy that typically infiltrates the surrounding tissue with malignant cells. It disrupts cerebral blood flow through a variety of biomechanical and biochemical mechanisms. Thus, neuroimaging focused on identifying regions of vascular dysregulation may reveal a marker of tumor spread. The purpose of this study was to use blood oxygenation level-dependent (BOLD) functional MRI (fMRI) to compare the temporal dynamics of the enhancing portion of a tumor with those of brain regions without apparent tumors. MATERIALS AND METHODS: Patients with pathologically proven glioblastoma underwent preoperative resting-state BOLD fMRI, T1-weighted contrast-enhanced MRI, and FLAIR MRI. The contralesional control hemisphere, contrast-enhancing tumor, and peritu-moral edema were segmented by use of structural images and were used to extract the time series of these respective regions. The parameter estimates (beta values) for the two regressors and resulting z-statistic images were used as a metric to compare the similarity of the tumor dynamics to those of other brain regions. RESULTS: The time course of the contrast-enhancing tumor was significantly different from that of the rest of the brain (p < 0.05). Similarly, the control signal intensity was significantly different from the tumor signal intensity (p < 0.05). Notably, the temporal dynamics in the peritumoral edema, which did not contain enhancing tumor, were most similar to the those of enhancing tumor than to those of control regions. CONCLUSION: The findings show that the disruption in vascular regulation induced by a glioblastoma can be detected with BOLD fMRI and that the spatial distribution of these disruptions is localized to the immediate vicinity of the tumor and peritumoral edema.

Acute Amnesia due to Isolated Mammillary Body Infarct.

BACKGROUND: There are limited reports describing acute amnesia after mammillothalamic tract infarction. Furthermore, acute infarction isolated to the mammillary body has never been reported. We present the first case of anterograde amnesia after isolated acute infarction of the mammillary body in a patient without concurrent or prior thalamic or mammillothalamic tract injury. METHODS: A retrospective review of the patient's electronic medical record including inpatient notes and all radiological examinations was performed. RESULTS: A 50-year-old woman presented with acute onset of confusion and constant repetition of the same questions. Magnetic resonance (MR) imaging of the brain showed isolated acute infarct of the left mammillary body without concurrent abnormality of the thalamus or mammillothalamic tract. MR angiography showed severe stenosis of the proximal posterior cerebral artery at the origin of the perforating mammillary artery. CONCLUSIONS: Isolated injury to the mammillary body is rare. In addition to recognized memory-related structures such as the thalamus and mammillothalamic tract, mammillary body injury may also play a role in memory dysfunction. Knowledge of the vascular supply of memory-related structures is important in diagnosing and understanding memory dysfunction.

Coincidental Optic Nerve Meningioma and Thyroid Eye Disease.

A 57-year-old woman with diabetes mellitus, hypertension, obesity, and Graves disease presented with clinical evidence of thyroid eye disease (TED) and optic neuropathy. She was referred when a tapered dose of steroids prompted worsening of her TED. CT and MRI were consistent with TED and bilateral optic nerve meningioma. To the authors' knowledge, this is the first reported case of concurrent TED and unsuspected bilateral optic nerve meningioma. When investigating the etiology of TED-associated optic neuropathy, careful attention to orbital imaging is required because coexisting pathology may exist.

Optic nerve glioma: case series with review of clinical, radiologic, molecular, and histopathologic characteristics.

PURPOSE: This study was designed to better understand the biologic nature of optic nerve gliomas (ONGs) and to investigate staining techniques that might improve the pathologic interpretation of surgical margins. METHODS: In this retrospective case series, clinical data on patient presentation, MRI, surgical visualization, and initial pathologic interpretation were gathered. Specimens were then reexamined using analysis of p53, isocitrate dehydrogenase 1 (IDH1), MIB-1, and B-rapidly accelerated fibrosarcoma (BRAF) duplication. RESULTS: Six patients were studied. All were diagnosed with World Health Organization grade 1 ONGs on original pathology. On reexamination, BRAF tandem duplication was found in 2 patients with neurofibromatosis Type 1 association. P53 immunoreactivity was noted in a third case. No cases had IDH1 immunoreactivity. Focal elevations of MIB-1 up to 7.5% were noted in 2 cases. CONCLUSIONS: ONGs are neoplasms with variable degrees of aggressiveness. As more is understood regarding their varied genetic underpinnings, improved pathologic classification and individualized treatment regimens may be achieved. The authors hope that this study helps guide the oculoplastic community toward a multi-institutional, prospective study of ONG genomic sequencing.

High response rates and prolonged survival in patients with corticotroph pituitary tumors and refractory Cushing disease from capecitabine and temozolomide (CAPTEM): a case series.

BACKGROUND AND IMPORTANCE: Rarely, corticotrophic pituitary tumors take on an aggressive form characterized by rapid growth, invasion into local structures, compression of cranial nerves, and possible spread to distant sites. When conventional surgery, radiation therapy, and hormones fail to control progression and symptoms, alternative therapies are needed. A novel chemotherapeutic regimen of capecitabine and temozolomide (CAPTEM), originally designed in our laboratory, demonstrated dramatic antineoplastic effects against corticotrophic pituitary tumors. CLINICAL PRESENTATION: We present a case series of 4 patients with aggressive, adrenocorticotrophic hormone--producing pituitary tumors who had previously depleted all surgical, radiation, and hormonal therapies and were then treated with CAPTEM. Dramatic clinical improvements in neurological deficits and Cushing symptoms were evident in all patients after treatment was initiated. Confirmed by radiographic imaging, 2 of 4 patients demonstrated complete regression of disease, 1 patient had a 75% regression, and the fourth patient has ongoing stable disease for > 4.5 years at the time of this writing. Immunohistochemical analysis of patients' tumor samples showed low O-methyguanyl methyltransferase expression and adequate levels of mismatch repair enzymes (MLH-1, MSH-2, MSH-6, and PMS-2), which are important for the in vivo efficacy of CAPTEM. CONCLUSION: This is the first report of prolonged antitumor response to and radiographic complete remissions as a result of CAPTEM in patients with aggressive pituitary tumors who had exhausted all other therapies.

Review of imaging techniques in the diagnosis and management of brain metastases.

Brain metastasis is one of the most common diagnoses encountered by neurologists, neurosurgeons, radiologists, and oncologists. The aim of this article is to review imaging modalities used in the diagnosis and follow-up of brain metastases. Through the use of various imaging techniques more accurate preoperative diagnosis and more precise intraoperative planning can be made. Post-treatment evaluation can also be refined through the use of these imaging techniques.