Central Nervous System Tumor With BCL6 Corepressor Internal Tandem Duplication: Treatment Course of a Long-term Survivor.

Central nervous system (CNS) tumor with BCL6 corepressor (BCOR) internal tandem duplication (ITD) is a newly described CNS tumor, characterized by in-frame ITDs of the BCOR gene. There is no standard practice regarding the management of this tumor. We report the clinical course of a 6-year-old boy who presented to the hospital with worsening headaches. Computed tomography scan showed a large right-sided parietal supratentorial mass and brain magnetic resonance imaging confirmed a 6×8×6.7 cm lobulated, solid but heterogeneous mass in the right parieto-occipital region. While initial pathology suggested a WHO grade 3 anaplastic meningioma, additional investigation with molecular analysis confirmed the diagnosis of high-grade neuroepithelial tumor with BCOR exon 15 ITD. This diagnosis was renamed CNS tumor with BCOR ITD in the 2021 WHO CNS tumor classification. The patient received 54 Gy of focal radiation and has no evidence of disease recurrence after 48 months from the end of treatment. As this is a newly discovered entity with only a few previous reports in the scientific literature, this report presents a unique treatment for this CNS tumor compared with those previously described.

Pineal Parenchymal Tumor of Intermediate Differentiation and DICER1 Syndrome: A Case Report.

DICER1 syndrome is a rare inherited tumor predisposition syndrome associated with an increased risk for several malignant and benign tumors. We present a patient with pineal parenchymal tumor of intermediate differentiation who was found to have a germline pathogenic variant in DICER1 gene. Pineoblastoma is a known DICER1-related tumor; however, the association between pineal parenchymal tumor of intermediate differentiation and DICER1 mutation is rare with only 1 recent large molecular study that has reported this association. This report adds to the evolving tumor spectrum of DICER1 and highlights the importance of molecular evaluation of pediatric brain tumors, for both therapeutic decisions and long-term surveillance.

Histopathology of new-onset refractory status epilepticus (NORSE) in adults.

OBJECTIVE: new-onset refractory status epilepticus (NORSE) is defined as de novo refractory seizures occurring in previously healthy adults, without a clear underlying etiology. Due to refractory seizures and insufficient understanding of pathophysiology, management of these patients remains challenging and often leads to poor clinical outcomes. Various infectious and autoimmune mechanisms have been proposed but have not been validated and a large number of patients are thus labeled 'cryptogenic'. Moreover, histopathological findings have rarely been described in NORSE and are usually autopsy evaluations. In this paper, we describe the clinical correlates and histopathological findings in patients presenting with NORSE. METHODS: A case series of five patients with NORSE who underwent neurosurgical intervention and had histopathological examination during their acute clinical course. RESULTS: In all patients,status epileptics was refractory to treatment with antiseizure drugs (ASDs) and anesthetic agents. Autoimmune work-up revealed elevated titer of anti-GAD antibody in one patient but was unremarkable in others. Empiric use of immunomodulation therapy in three patients did not lead to cessation of status epilepticus (SE). Due to failure of prolonged medical management, three patients underwent palliative surgery for resection of epileptogenic tissue whereas the other two had diagnostic brain biopsy. Histopathology obtained during biopsy revealed evidence of vasculitis in one and necrotizing vasculopathy in another. The patient with anti-GAD antibodies had evidence of lymphocytic infiltration in limbic structures. The remaining two had nonspecific histopathological findings. SIGNIFICANCE: Although our findings are limited by a small number of patients, it adds to the growing premise of NORSE being related to an underlying autoimmune process. Additional studies, especially with histopathological data are needed to better understand this devastating disorder.

Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors.

INTRODUCTION: There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment. METHODS: We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), as well as, the aryl hydrocarbon receptor (AhR), a carcinogenic transcription factor activated by KP metabolites. In addition, we utilized commercially available small-molecules to pharmacologically modulate IDO1, IDO2, TDO2, and AhR in patient-derived glioma and meningioma cell lines (n = 9 each). RESULTS: We observed a positive trend between the grade of the tumor and the average immunohistochemical staining score for IDO1, IDO2, and TDO2, with TDO2 displaying the strongest immunostaining. AhR immunostaining was present in all grades of gliomas and meningiomas, with the greatest staining intensity noted in glioblastomas. Immunocytochemical staining showed a positive trend between nuclear localization of AhR and histologic grade in both gliomas and meningiomas, suggesting increased AhR activation with higher tumor grade. Unlike enzyme inhibition, AhR antagonism markedly diminished patient-derived tumor cell viability, regardless of tumor type or grade, following in vitro drug treatments. CONCLUSIONS: Collectively, these results suggest that AhR may offer a novel and robust therapeutic target for a patient population with highly limited treatment options.

Acute Resective Surgery for the Treatment of Refractory Status Epilepticus.

BACKGROUND: To identify the role of acute surgical intervention in the treatment of refractory status epilepticus (RSE). METHODS: Retrospective review of consecutive patients who underwent epilepsy surgery from 2006 to 2015 was done to identify cases where acute surgical intervention was employed for the treatment of RSE. In addition, the adult and pediatric RSE literature was reviewed for reports of surgical treatment of RSE. RESULTS: Nine patients, aged 20-68 years, with various etiologies were identified to have undergone acute surgical resection for the treatment of RSE, aided by electrocorticography. Patients required aggressive medical therapy with antiepileptic drugs and intravenous anesthetic drugs for 10-54 days and underwent extensive neurodiagnostic testing prior to resective surgery. Eight out of nine patients survived and five patients were seizure-free at the last follow-up. The literature revealed 13 adult and 48 pediatric cases where adequate historical detail was available for review and comparison. CONCLUSIONS: We present the largest cohort of consecutive adult patients who underwent resective surgery in the setting of RSE. We also reveal that surgery can be efficacious in aborting status and in some can lead to long-term seizure freedom. Acute surgical intervention is a viable option in prolonged RSE and proper evaluation for such intervention should be conducted, although the timing and type of surgical intervention remain poorly defined.

Tryptophan PET Imaging of the Kynurenine Pathway in Patient-Derived Xenograft Models of Glioblastoma.

Increasing evidence demonstrates the immunosuppressive kynurenine pathway's (KP) role in the pathophysiology of human gliomas. To study the KP in vivo, we used the noninvasive molecular imaging tracer α-[(11)C]-methyl-l-tryptophan (AMT). The AMT-positron emission tomography (PET) has shown high uptake in high-grade gliomas and predicted survival in patients with recurrent glioblastoma (GBM). We generated patient-derived xenograft (PDX) models from dissociated cells, or tumor fragments, from 5 patients with GBM. Mice bearing subcutaneous tumors were imaged with AMT-PET, and tumors were analyzed to detect the KP enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, tryptophan 2,3-dioxygenase, kynureninase, and kynurenine 3-monooxygenase. Overall, PET imaging showed robust tumoral AMT uptake in PDX mice with prolonged tracer accumulation over 60 minutes, consistent with AMT trapping seen in humans. Immunostained tumor tissues demonstrated positive detection of multiple KP enzymes. Furthermore, intracranial implantation of GBM cells was performed with imaging at both 9 and 14 days postimplant, with a marked increase in AMT uptake at 14 days and a corresponding high level of tissue immunostaining for KP enzymes. These results indicate that our PDX mouse models recapitulate human GBM, including aberrant tryptophan metabolism, and offer an in vivo system for development of targeted therapeutics for patients with GBM.

Surgical treatment for refractory epileptic spasms: The Detroit series.

OBJECTIVE: We reviewed our experience of surgery for epileptic spasms (ES) with or without history of infantile spasms. METHODS: Data were reviewed from 65 (33 male) patients with ES who underwent surgery between 1993 and 2014; palliative cases were excluded. RESULTS: Mean age at surgery was 5.1 (range 0.2-19) years, with mean postsurgical follow-up of 45.3 (6-120) months. Mean number of anticonvulsants used preoperatively was 4.2 (2-8), which decreased to 1.2 (0-4) postoperatively (p < 0.0001). Total hemispherectomy was the most commonly performed surgery (n = 20), followed by subtotal hemispherectomy (n = 17), multilobar resection (n = 13), lobectomy (n = 7), tuberectomy (n = 6), and lobectomy + tuberectomy (n = 2), with International League Against Epilepsy (ILAE) class I outcome in 20, 10, 7, 6, 3, and 0 patients, respectively (total 46/65 (71%); 22 off medication). Shorter duration of epilepsy (p = 0.022) and presence of magnetic resonance imaging (MRI) lesion (p = 0.026) were independently associated with class I outcome. Of 34 patients operated <3 years after seizure onset, 30 (88%) achieved class I outcome. Thirty-seven (79%) of 47 patients with lesional MRI had class-I outcome, whereas 9 (50%) of 18 with normal MRI had class I outcome. Positron emission tomography (PET) scan was abnormal in almost all patients [61 (97%) of 63 with lateralizing/localizing findings in 56 (92%) of 61 patients, thus helping in surgical decision making and guiding subdural grid placements, particularly in patients with nonlesional MRI. Fifteen patients had postoperative complications, mostly minor. SIGNIFICANCE: Curative epilepsy surgery in ES patients, with or without history of infantile spasms, is best accomplished at an early age and in those patients with lesional abnormalities on MRI with electroencephalography (EEG) concordance. Good outcomes can be achieved even when there is no MRI lesion but positive PET localization.

Multi-modal imaging of tumor cellularity and Tryptophan metabolism in human Gliomas.

BACKGROUND: To assess gliomas using image-based estimation of cellularity, we utilized isotropic diffusion spectrum imaging (IDSI) on clinically feasible diffusion tensor imaging (DTI) and compared it with amino acid uptake measured by α[(11)C]methyl-L-tryptophan positron emission tomography (AMT-PET). METHODS: In 10 patients with a newly-diagnosed glioma, metabolically active tumor regions were defined in both FLAIR hyperintense areas and based on increased uptake on AMT-PET. A recently developed independent component analysis with a ball and stick model was extended to perform IDSI in clinical DTI data. In tumor regions, IDSI was used to define tumor cellularity which was compared between low and high grade glioma and correlated with the glioma proliferative index. RESULTS: The IDSI-derived cellularity values were elevated in both FLAIR and AMT-PET-derived regions of high-grade gliomas. ROC curve analysis found that the IDSI-derived cellularity can provide good differentiation of low-grade from high-grade gliomas (accuracy/sensitivity/specificity of 0.80/0.80/0.80). . Both apparent diffusion coefficient (ADC) and IDSI-derived cellularity showed a significant correlation with the glioma proliferative index (based on Ki-67 labeling; R = 0.95, p < 0.001), which was particularly strong when the tumor regions were confined to areas with high tryptophan uptake excluding areas with peritumoral edema. CONCLUSION: IDSI-MRI combined with AMT-PET may provide a multi-modal imaging tool to enhance pretreatment assessment of human gliomas by evaluating tumor cellularity and differentiate low-grade form high-grade gliomas.

Molecular imaging correlates of tryptophan metabolism via the kynurenine pathway in human meningiomas.

BACKGROUND: Increased tryptophan metabolism via the kynurenine pathway (KP) is a key mechanism of tumoral immune suppression in gliomas. However, details of tryptophan metabolism in meningiomas have not been elucidated. In this study, we evaluated in vivo tryptophan metabolism in meningiomas and compared it with gliomas using α-[(11)C]-methyl-L-tryptophan (AMT)-PET. We also explored expression patterns of KP enzymes in resected meningiomas. METHODS: Forty-seven patients with MRI-detected meningioma (n = 16) and glioma (n = 31) underwent presurgical AMT-PET scanning. Tumoral AMT uptake and tracer kinetic parameters (including K and k3' evaluating unidirectional uptake and trapping, respectively) were measured, correlated with meningioma grade, and compared between meningiomas and gliomas. Patterns of KP enzyme expression were assessed by immunohistochemistry in all meningiomas. RESULTS: Meningioma grade showed a positive correlation with AMT k3' tumor/cortex ratio (r = 0.75, P = .003), and this PET parameter distinguished grade I from grade II/III meningiomas with 92% accuracy. Kinetic AMT parameters could differentiate meningiomas from both low-grade gliomas (97% accuracy by k3' ratios) and high-grade gliomas (83% accuracy by K ratios). Among 3 initial KP enzymes (indoleamine 2,3-dioxygenase 1/2, and tryptophan 2,3-dioxygenase 2 [TDO2]), TDO2 showed the strongest immunostaining, particularly in grade I meningiomas. TDO2 also showed a strong negative correlation with AMT k3' ratios (P = .001). CONCLUSIONS: PET imaging of tryptophan metabolism can provide quantitative imaging markers for differentiating grade I from grade II/III meningiomas. TDO2 may be an important driver of in vivo tryptophan metabolism in these tumors. These results can have implications for pharmacological targeting of the KP in meningiomas.

Acute thymic involution in unexplained third trimester stillbirth: frequency, grade, and correlation with neuropathologic injury.

Many 3rd-trimester stillbirths are unexplained, including the time course of the illness. Histologic acute thymic involution (ATI), when graded, correlates with duration of acute illness (grade 0, <12 hours; grade 4, >72 hours). Histologic brain injury is also common in stillbirth. We investigated ATI in unexplained stillbirth and correlated it with neuropathologic injury by identifying 58 autopsies of unexplained, 3rd-trimester stillborns (preterm, n  =  24; term, n  =  34) that included brain examination and graded ATI from 0 (resting state) to 4 (pronounced lymphodepletion). Gray matter injury (GMI) and white matter injury (WMI) were classified as older, recent, or absent, and ATI was correlated with GMI, WMI, thymic weight, and clinical data. Nine cases (16%) had ATI grade 0-1; 19 (33%), grade 2; 24 (41%), grade 3; and 6 (10%), grade 4. Older GMI and WMI were present in 39 (67%) and 10 (17%) stillborns, respectively. Higher ATI grade correlated significantly with older GMI (P < 0.001) and WMI (P  =  0.014). The ATI grade was higher in the small-for-gestational stillborns compared with the appropriate- or large-for-gestational stillborns (P  =  0.017) but did not correlate significantly with gestational age or other clinical or demographic factors evaluated. The ATI grades 2-4 were found in 84% of the stillborns, consistent with onset of acute illness between 24 and >72 hours before demise. Higher ATI grade correlated significantly with older brain injury, suggesting similar time of onset and shared underlying pathophysiologic events, the specific nature of which remains unclear.

Antenatal brain injury in third trimester neonates with severe congenital anomalies: an autopsy study.

OBJECTIVE: With advances in therapy, more neonates with severe congenital anomalies are surviving, albeit some with neurologic disorders, possibly related to antenatal low brain blood flow. This autopsy series reports antenatal brain injury in neonates expiring due to severe anomalies, and provides correlation with umbilical cord blood gas and acid-base analysis. METHODS: We identified autopsies of third trimester neonates expiring shortly following delivery due to severe anomalies or malformations. Brain injury classified as "older" included periventricular leukomalacia, gliosis and karyorrhectic neurons, and "recent" included red neurons and reactive glial changes. RESULTS: We identified 22 cases (nine term, 13 preterm). 16 (73%) had brain injury, including 11 with older injury. Cord arterial blood was analyzed in 17, and six had pH <7 or base deficit >12 mmol/L. Four out of 5 (80%) neonates with neuronal necrosis compared to two out of 12 (17%) without had a pH <7 or base deficit >12 mmol/L (p = 0.03). Five out of nine (56%) neonates with white matter injury compared to one out of 8 (13%) without had pH <7 or base deficit >12 mmol/L (p = NS). CONCLUSIONS: Antenatal brain injury is frequent in neonates with severe congenital anomalies. Severely abnormal cord blood analysis results correlate significantly with neuronal necrosis and show a trend toward white matter injury; however, the absence of these abnormal results does not preclude the presence of brain injury.

"Subtotal" hemispherectomy in children with intractable focal epilepsy.

OBJECTIVE: Cortical resections in epilepsy surgery tend to be larger in children, compared to adults, partly due to underlying pathology. Some children show unilateral multifocal seizure onsets involving much of the hemisphere. If there were a significant hemiparesis present, hemispherectomy would be the procedure of choice. Otherwise, it is preferable to spare the primary sensorimotor cortex. We report the results of "subtotal" hemispherectomy in 23 children. METHODS: All children (ages 1 year and 4 months to 14 years and 2 months) were operated on between 2001 and 2013 at Children's Hospital of Michigan (Detroit). Patients were evaluated with scalp video-electroencephalography (EEG), magnetic resonance imaging (MRI), (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scans, and neuropsychological assessments when applicable. Subsequently, each case was discussed in a multidisciplinary epilepsy surgery conference, and a consensus was reached pertaining to candidacy for surgery and optimum surgical approach. The actual extent of resection was based on the results from subdural electrocorticography (ECoG) monitoring. The surgical outcome is based on International League Against Epilepsy (ILAE) classification (class 1-6). RESULTS: Among the 23 patients, 11 had epileptic spasms as their major seizure type; these were associated with focal seizures in 3 children. MRI showed focal abnormalities in 12 children. FDG-PET was abnormal in all but one subject. All except two children underwent chronic subdural ECoG. Multiple subpial transections were performed over the sensorimotor cortex in three subjects. On histopathology, various malformations were seen in 9 subjects; the remainder showed gliosis alone (n = 12), porencephaly (n = 1), and gliosis with microglial activation (n = 1). Follow-up ranged from 13 to 157 months (mean = 65 months). Outcomes consisted of class 1 (n = 17, 74%), class 2 (n = 2), class 3 (n = 1), class 4 (n = 1), and class 5 (n = 2). SIGNIFICANCE: Extensive unilateral resections sparing only sensorimotor cortex can be performed with excellent results in seizure control. Even with the presence of widespread unilateral epileptogenicity or anatomic/functional imaging abnormalities, complete hemispherectomy can often be avoided, particularly when there is little hemiparesis.

Spontaneous intratumoral infarction--an unusual evolution of a falcine meningioma.

OBJECTIVE: We report the incidence of spontaneous infarction of a falcine meningioma without preceding hemorrhage and shed light on the relation between intratumoral necrosis and hemorrhage. CLINICAL PRESENTATION: A 50 year-old woman presented with recurrent headaches and was found to harbor a falcine meningioma. The patient elected to observe the mass and 13 months later she developed new neurological deficits. Prior to scheduled resection, she presented with abdominal pain and underwent emergent laparoscopic cholecystectomy. Two days after the procedure, she developed sudden right hemiparesis associated with severe headache. MRI of the brain showed an intratumoral wedge-shaped hypointense area with significant peritumoral edema. The patient was started on high-dose corticosteroids with considerable improvement in strength. INTERVENTION: The patient underwent a complete resection of the tumor with no new neurological deficits post-operatively. Histopathological analysis confirmed a WHO grade II atypical meningioma with extensive necrosis without hemorrhage. CONCLUSION: This case highlights that tumor infarction, although rare, should be in the differential diagnosis of patients with meningiomas presenting with new neurological deficits. When this condition is recognized and treated in timely manner with high-dose corticosteroids and surgical resection, patients can have favorable long-term outcomes.

Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma.

BACKGROUND: Previously, we demonstrated the high accuracy of alpha-[(11)C]methyl-L-tryptophan (AMT) PET for differentiating recurrent gliomas from radiation injury. The present study evaluated the prognostic value of increased AMT uptake in patients with previously treated high-grade glioma. METHODS: AMT-PET was performed in 39 patients with suspected recurrence of World Health Organization grades III-IV glioma following surgical resection, radiation, and chemotherapy. Mean and maximum standardized uptake values (SUVs) and unidirectional AMT uptake (K) were measured in brain regions suspicious for tumor and compared with the contralateral cortex (ie, background). Optimal cutoff thresholds for 1-year survival prediction were determined for each AMT parameter and used for calculating the prognostic value of high (above threshold) versus low (below threshold) values for post-PET overall survival (OS). RESULTS: In univariate analyses, 1-year survival was strongly associated with 3 AMT parameters (SUVmax, SUVmean, and tumor-to-background K-ratio; odds ratios: 21.3-25.6; P ≤ .001) and with recent change in MRI contrast enhancement (odds ratio: 14.7; P = .02). Median OS was 876 days in the low- versus 177 days in the high-AMT groups (log-rank P < .001). In multivariate analyses, all 3 AMT parameters remained strong predictors of survival: high AMT values were associated with unfavorable 1-year survival (binary regression P ≤ .003) and shorter overall survival in the whole group (Cox regression hazard ratios: 5.3-10.0) and in patients with recent enhancement change on MRI as well (hazard ratios: 7.0-9.3; P ≤ .001). CONCLUSION: Increased AMT uptake on PET is highly prognostic for 1-year and overall survival, independent of MRI contrast enhancement and other prognostic factors in patients with a previously treated high-grade glioma.

Third trimester fetal demise occurring at time of delivery: correlation of autopsy findings and placental pathology with emphasis on antenatal central nervous system injury.

OBJECTIVE: Third trimester fetal deaths occurring in the hospital at the time of delivery are unusual. We report an autopsy series of such cases with emphasis on neuropathological injury and other lesions predating delivery. METHODS: We identified autopsies performed on third trimester fetuses documented to be alive shortly before delivery, but that expired during, or very close to, time of delivery, and we correlate autopsy and placental findings. Fetuses with major congenital anomalies were excluded. RESULTS: Ten cases were identified (6 term, 4 preterm). All were delivered by cesarean section and had attempted resuscitation. Established or recent brain injury was identified in 9 of 10 cases, including 3 with established neuronal damage and 1 with periventricular leukomalacia. Additional autopsy findings included thymic involution in eight (five mild; three severe), myocardial infarcts in two; intrathoracic petechiae in five, and ascites or pleural or pericardial effusions in six. Severe thymic involution and myocardial infarcts correlated with established brain injury. Placental lesions adaptive to decreased oxygenation (increased nucleated red blood cells or villous hypervascularity) were seen in five cases and correlated with established brain injury. Acute chorioamnionitis with funisitis was present in one, and chronic inflammatory placental lesions were present in six. CONCLUSIONS: These findings indicate brain injury predated the time period immediately before delivery in 9 of 10 fetuses, and in the fetuses with established brain injury the onset of acute illness was possibly >72 h before delivery.

Histopathological evidence that hippocampal atrophy following status epilepticus is a result of neuronal necrosis.

Medial temporal lobe epilepsy is commonly associated with hippocampal atrophy on MRI and hippocampal sclerosis on histopathological examination of surgically-resected specimens. Likewise, it is well-established that prolonged seizures and status epilepticus can lead to hippocampal edema as noted on MRI. In this paper, the authors present an unusual patient with prolonged refractory status epilepticus, due to limbic encephalitis associated with anti-GAD antibody, who underwent palliative epilepsy surgery. Bilateral hippocampal edema was noted on preoperative MRI. Histologic evaluation confirmed presence of acute necrosis and neuronal loss in the left hippocampal formation. Follow-up MRI several months after surgery demonstrated severe atrophy of the contralateral right hippocampus. This is the first clear histopathological evidence that hippocampal atrophy following status epilepticus is the result of acute neuronal necrosis and cell loss.

Successful surgical treatment of an inflammatory lesion associated with new-onset refractory status epilepticus.

New-onset refractory status epilepticus (NORSE) has high morbidity and mortality. The authors describe the successful surgical treatment of a 56-year-old man presenting with NORSE. Magnetic resonance imaging showed a left temporal lobe lesion suspicious for a low-grade tumor, while PET imaging with the alpha[(11)C]methyl-L-tryptophan (AMT) radiotracer showed increased cortical uptake extending beyond this lesion and partly overlapping with epileptogenic cortex mapped by chronic intracranial electroencephalographic monitoring. Resection of the epileptic focus resulted in long-term seizure freedom, and the nonresected portion of the PET-documented abnormality normalized. Histopathology showed reactive gliosis and inflammatory markers in the AMT-PET-positive cortex. Molecular imaging of neuroinflammation can be instrumental in the management of NORSE by guiding placement of intracranial electrodes or assessing the extent and severity of inflammation for antiinflammatory interventions.

Differentiation of glioblastomas from metastatic brain tumors by tryptophan uptake and kinetic analysis: a positron emission tomographic study with magnetic resonance imaging comparison.

Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional magnetic resonance imaging (MRI); molecular imaging may facilitate such discrimination. We tested the accuracy of α[11C]methyl-l-tryptophan (AMT)-positron emission tomography (PET) to differentiate newly diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs). Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution [VD]) from unidirectional uptake rates using dynamic PET and blood input function. Differentiating the accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74%) and the tumor/cortex VD ratio had the highest positive predictive value (82%). The combined accuracy of MRI (size of contrast-enhancing lesion) and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with > 90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pretreatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly diagnosed solitary ring-enhancing mass.