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1.
J Comput Assist Tomogr ; 47(4): 613-620, 2023.
Article in English | MEDLINE | ID: mdl-37380149

ABSTRACT

ABSTRACT: Photon-counting computed tomography (PCCT) offers better high-resolution and noise performance than energy integrating detector (EID) CT. In this work, we compared both technologies for imaging of the temporal bone and skull base. A clinical PCCT system and 3 clinical EID CT scanners were used to image the American College of Radiology image quality phantom using a clinical imaging protocol with matched CTDI vol (CT dose index-volume) of 25 mGy. Images were used to characterize the image quality of each system across a series of high-resolution reconstruction options. Noise was calculated from the noise power spectrum, whereas resolution was quantified with a bone insert by calculating a task transfer function. Images of an anthropomorphic skull phantom and 2 patient cases were examined for visualization of small anatomical structures. Across measured conditions, PCCT had a comparable or smaller average noise magnitude (120 Hounsfield units [HU]) to the EID systems (144-326 HU). Photon-counting CT also had comparable resolution (task transfer function f25 : 1.60 mm -1 ) to the EID systems (1.34-1.77 mm -1 ). Imaging results supported quantitative findings as PCCT more clearly showed the 12-lp/cm bars from the fourth section of the American College of Radiology phantom and better represented the vestibular aqueduct and oval and round windows when compared with the EID scanners. A clinical PCCT system was able to image the temporal bone and skull base with improved spatial resolution and lower noise than clinical EID CT systems at matched dose.


Subject(s)
Head , Tomography, X-Ray Computed , Humans , Tomography, X-Ray Computed/methods , Tomography Scanners, X-Ray Computed , Phantoms, Imaging , Skull Base/diagnostic imaging , Photons
2.
Sci Transl Med ; 15(682): eabn5649, 2023 02 08.
Article in English | MEDLINE | ID: mdl-36753564

ABSTRACT

D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized that immunosuppression in glioblastoma limits D2C7-IT efficacy. To improve the response rate and reverse immunosuppression, we combined D2C7-IT tumor cell killing with αCD40 costimulation of antigen-presenting cells. In murine glioma models, a single intratumoral injection of D2C7-IT+αCD40 treatment activated a proinflammatory phenotype in microglia and macrophages, promoted long-term tumor-specific CD8+ T cell immunity, and generated cures. D2C7-IT+αCD40 treatment increased intratumoral Slamf6+CD8+ T cells with a progenitor phenotype and decreased terminally exhausted CD8+ T cells. D2C7-IT+αCD40 treatment stimulated intratumoral CD8+ T cell proliferation and generated cures in glioma-bearing mice despite FTY720-induced peripheral T cell sequestration. Tumor transcriptome profiling established CD40 up-regulation, pattern recognition receptor, cell senescence, and immune response pathway activation as the drivers of D2C7-IT+αCD40 antitumor responses. To determine potential translation, immunohistochemistry staining confirmed CD40 expression in human GBM tissue sections. These promising preclinical data allowed us to initiate a phase 1 study with D2C7-IT+αhCD40 in patients with malignant glioma (NCT04547777) to further evaluate this treatment in humans.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Immunotoxins , Humans , Animals , Mice , Glioblastoma/pathology , Immunotoxins/genetics , CD8-Positive T-Lymphocytes , Adaptive Immunity , ErbB Receptors/metabolism , Cell Line, Tumor , Brain Neoplasms/therapy
3.
J Vasc Interv Radiol ; 33(12): 1594-1600, 2022 12.
Article in English | MEDLINE | ID: mdl-36007783

ABSTRACT

PURPOSE: To measure the ablation zone temperature and nontarget tissue temperature during radiofrequency (RF) ablation in bone containing metal instrumentation versus no metal instrumentation (control group). MATERIALS AND METHODS: Ex vivo experiments were performed on 15 swine vertebrae (control, n = 5; titanium screw, n = 5; stainless steel screw, n = 5). Screws and RF ablation probe were inserted identically under fluoroscopy. During RF ablation (3 W, 5 minutes), temperature was measured 10 mm from RF ablation centerpoint and in muscle contacting the screw. Magnetic resonance (MR) imaging, gross pathologic, and histopathologic analyses were performed on 1 specimen from each group. RESULTS: Ablation zone temperatures at 2.5 and 5 minutes increased by 12.2 °C ± 2.6 °C and 21.5 °C ± 2.1 °C (control); 11.0 °C ± 4.1 °C and 20.0 °C ± 2.9 °C (juxta-titanium screw), and 10.0 °C ± 3.4 °C and 17.2 °C ± 3.5 °C (juxta-stainless steel) screw; differences among groups did not reach significance by analysis of variance (P = .87). Mixed-effects linear regression revealed a statistically significant increase in temperature over time in all 3 groups (4.2 °C/min ± 0.4 °C/min, P < .001). Compared with the control, there was no significant difference in the temperature change over time for titanium (-0.3 °C/min ± 0.5 °C/min, P = .53) or steel groups (-0.4 °C/min ± 0.5 °C/min, P = .38). The mean screw temperature at the final time point did not show a statistically significant change compared with baseline in either the titanium group (-1.2 °C ± 2.3 °C, P = .50) or steel group (2.6 °C ± 2.9 °C, P = .11). MR imaging and pathologic analyses revealed homogeneous ablation without sparing of the peri-hardware zones. CONCLUSIONS: Adjacent metallic instrumentation did not affect the rate of or absolute increase in temperature in the ablation zone, did not create peri-metallic ablation inhomogeneities, and did not result in significant nontarget heating of muscle tissue in contact with the metal instrumentation.


Subject(s)
Catheter Ablation , Stainless Steel , Swine , Animals , Titanium , Catheter Ablation/methods , Liver/surgery , Magnetic Resonance Imaging
4.
Clin Imaging ; 85: 14-21, 2022 May.
Article in English | MEDLINE | ID: mdl-35228170

ABSTRACT

PURPOSE: To evaluate patient outcomes after sacroplasty (percutaneous sacral augmentation) with guidance using CT compared to fluoroscopy with augmented reality overlay using fluoroscopic cone-beam CT and FDA-approved software (CBCT-AF). MATERIALS AND METHODS: Retrospective IRB-approved study of all patients undergoing sacroplasty between 3/2019-9/2020 was performed. Procedural details were collected including whether the procedure was performed with CT-fluoroscopic guidance versus cone beam CT with vector navigation and real-time neuroforaminal contour overlay. Clinical details collected included Visual Analogue Scale (VAS) pain scores within 6-months post intervention. Images were analyzed on PACS to measure exact volumes of implanted cement. RESULTS: Twelve patients underwent sacroplasty using either CT (n = 13 hemisacra) or CBCT-AF (n = 10 hemisacra). No clinically significant complications occurred. Comparing CT versus CBCT-AF guidance there was no significant difference in radiation dose (CBCT-AF trended toward lower dose, p = 0.20), total anesthesia time (p = 0.71), or infused cement volume (p = 0.21). VAS pain scores decreased an average of 6.14 and 5.25 points for the CT and CBCT-AF groups respectively (p = 0.46, no significant difference between groups). CONCLUSION: Sacroplasty improved back pain in all patients, while CBCT-AF safely provided similar outcomes with trends toward lower radiation dose and cement volume compared to CT-fluoroscopy.


Subject(s)
Augmented Reality , Spinal Fractures , Vertebroplasty , Cone-Beam Computed Tomography/methods , Fluoroscopy/methods , Humans , Retrospective Studies , Sacrum , Treatment Outcome , Vertebroplasty/adverse effects , Vertebroplasty/methods
5.
Pediatr Radiol ; 51(10): 1895-1906, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33950270

ABSTRACT

BACKGROUND: Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of gadolinium-based contrast agents due to the immaturity of their body functions. OBJECTIVE: To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age. MATERIALS AND METHODS: One hundred twenty-five children ≤2 years old (including 57 children <6 months old) who underwent contrast-enhanced MRI of the CNS with gadoteridol at 0.1 mmol/kg body weight were retrospectively enrolled at five imaging centers. Safety data were assessed for acute/subacute adverse events in the 48 h following gadoteridol administration and, when available, vital signs, electrocardiogram (ECG) and clinical laboratory values obtained from blood samples taken from 48 h before until 48 h following the MRI exam. The efficacy of gadoteridol-enhanced MRI compared to unenhanced MRI for disease diagnosis was evaluated prospectively by three blinded, unaffiliated readers. RESULTS: Thirteen changes of laboratory values (11 mild, 1 moderate, 1 unspecified) were reported as adverse events in 7 (5.6%) patients. A relationship to gadoteridol was deemed possible though doubtful for two of these adverse events in two patients (1.6%). There were no clinical adverse events, no serious adverse events and no clinically meaningful changes in vital signs or ECG recordings. Accurate differentiation of tumor from non-neoplastic disease, and exact matching of specific MRI-determined diagnoses with on-site final diagnoses, was achieved in significantly more patients by each reader following the evaluation of combined pre- and post-contrast images compared to pre-contrast images alone (84.6-88.0% vs. 70.9-76.9%; P≤0.006 and 67.5-79.5% vs. 47.0-66.7%; P≤0.011, respectively). CONCLUSION: Gadoteridol at 0.1 mmol/kg body weight is safe, well tolerated and effective for contrast-enhanced MRI of the CNS in children ≤2 years of age.


Subject(s)
Brain Neoplasms , Heterocyclic Compounds , Organometallic Compounds , Brain , Child, Preschool , Contrast Media/adverse effects , Gadolinium/adverse effects , Heterocyclic Compounds/adverse effects , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Organometallic Compounds/adverse effects , Retrospective Studies
7.
Lancet Oncol ; 20(7): 1011-1022, 2019 07.
Article in English | MEDLINE | ID: mdl-31151904

ABSTRACT

BACKGROUND: Paediatric low-grade glioma is the most common CNS tumour of childhood. Although overall survival is good, disease often recurs. No single universally accepted treatment exists for these patients; however, standard cytotoxic chemotherapies are generally used. We aimed to assess the activity of selumetinib, a MEK1/2 inhibitor, in these patients. METHODS: The Pediatric Brain Tumor Consortium performed a multicentre, phase 2 study in patients with paediatric low-grade glioma in 11 hospitals in the USA. Patients aged 3-21 years with a Lansky or Karnofsky performance score greater than 60 and the presence of recurrent, refractory, or progressive paediatric low-grade glioma after at least one standard therapy were eligible for inclusion. Patients were assigned to six unique strata according to histology, tumour location, NF1 status, and BRAF aberration status; herein, we report the results of strata 1 and 3. Stratum 1 comprised patients with WHO grade I pilocytic astrocytoma harbouring either one of the two most common BRAF aberrations (KIAA1549-BRAF fusion or the BRAFV600E [Val600Glu] mutation). Stratum 3 comprised patients with any neurofibromatosis type 1 (NF1)-associated paediatric low-grade glioma (WHO grades I and II). Selumetinib was provided as capsules given orally at the recommended phase 2 dose of 25 mg/m2 twice daily in 28-day courses for up to 26 courses. The primary endpoint was the proportion of patients with a stratum-specific objective response (partial response or complete response), as assessed by the local site and sustained for at least 8 weeks. All responses were reviewed centrally. All eligible patients who initiated treatment were evaluable for the activity and toxicity analyses. Although the trial is ongoing in other strata, enrolment and planned follow-up is complete for strata 1 and 3. This trial is registered with ClinicalTrials.gov, number NCT01089101. FINDINGS: Between July 25, 2013, and June 12, 2015, 25 eligible and evaluable patients were accrued to stratum 1, and between Aug 28, 2013, and June 25, 2015, 25 eligible and evaluable patients were accrued to stratum 3. In stratum 1, nine (36% [95% CI 18-57]) of 25 patients achieved a sustained partial response. The median follow-up for the 11 patients who had not had a progression event by Aug 9, 2018, was 36·40 months (IQR 21·72-45·59). In stratum 3, ten (40% [21-61]) of 25 patients achieved a sustained partial response; median follow-up was 48·60 months (IQR 39·14-51·31) for the 17 patients without a progression event by Aug 9, 2018. The most frequent grade 3 or worse adverse events were elevated creatine phosphokinase (five [10%]) and maculopapular rash (five [10%]). No treatment-realted deaths were reported. INTERPRETATION: Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma. These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1. FUNDING: National Cancer Institute Cancer Therapy Evaluation Program, the American Lebanese Syrian Associated Charities, and AstraZeneca.


Subject(s)
Benzimidazoles/therapeutic use , Central Nervous System Neoplasms/drug therapy , Glioma/drug therapy , Adolescent , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/pathology , Child , Child, Preschool , Disease Progression , Female , Glioma/genetics , Glioma/pathology , Humans , Male , Neoplasm Grading , Neoplasms, Multiple Primary/pathology , Neurofibromatosis 1/pathology , Proto-Oncogene Proteins B-raf/genetics , Young Adult
8.
J Am Coll Radiol ; 16(3): 295-301, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30082238

ABSTRACT

Patient-centric care has garnered the attention of the radiology community. The authors describe a patient-centric approach to iodinated contrast administration designed to optimize the diagnostic yield of contrast-enhanced CT while minimizing patient iodine load and exposure to ionizing radiation, thereby enhancing patient safety while providing reasonable diagnostic efficacy. Patient-centric CT hardware settings and contrast media administration are important considerations for clinical CT quality and safety.


Subject(s)
Contrast Media/administration & dosage , Patient Safety , Patient-Centered Care , Tomography, X-Ray Computed , Humans , Radiation Exposure , Radiation Protection/methods
9.
Mol Genet Metab ; 123(2): 85-91, 2018 02.
Article in English | MEDLINE | ID: mdl-29050825

ABSTRACT

BACKGROUND: Recombinant human acid α-glucosidase (rhGAA) enzyme replacement therapy (ERT) has prolonged survival in infantile Pompe disease (IPD), but has unmasked central nervous system (CNS) changes. METHODS: Brain imaging, consisting of computed tomography (CT) and/or magnetic resonance imaging (MRI), was performed on 23 patients with IPD (17 CRIM-positive, 6 CRIM-negative) aged 2-38months. Most patients had baseline neuroimaging performed prior to the initiation of ERT. Follow-up neuroimaging was performed in eight. RESULTS: Sixteen patients (70%) had neuroimaging abnormalities consisting of ventricular enlargement (VE) and/or extra-axial cerebrospinal fluid accumulation (EACSF) at baseline, with delayed myelination in two. Follow-up neuroimaging (n=8) after 6-153months showed marked improvement, with normalization of VE and EACSF in seven patients. Two of three patients imaged after age 10years demonstrated white matter changes, with one noted to have a basilar artery aneurysm. CONCLUSIONS: Mild abnormalities on brain imaging in untreated or newly treated patients with IPD tend to resolve with time, in conjunction with ERT. However, white matter changes are emerging as seen in Patients 1 and 3 which included abnormal periventricular white matter changes with subtle signal abnormalities in the basal ganglia and minimal, symmetric signal abnormalities involving the deep frontoparietal cerebral white matter, respectively. The role of neuroimaging as part of the clinical evaluation of IPD needs to be considered to assess for white matter changes and cerebral aneurysms.


Subject(s)
Brain/diagnostic imaging , Enzyme Replacement Therapy , Glycogen Storage Disease Type II/diagnostic imaging , Glycogen Storage Disease Type II/therapy , Neuroimaging/methods , alpha-Glucosidases/administration & dosage , Adolescent , Child , Child, Preschool , Female , Glycogen Storage Disease Type II/enzymology , Humans , Infant , Male , Treatment Outcome
10.
J Magn Reson Imaging ; 41(2): 296-313, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24817252

ABSTRACT

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) is used to track the first pass of an exogenous, paramagnetic, nondiffusible contrast agent through brain tissue, and has emerged as a powerful tool in the characterization of brain tumor hemodynamics. DSC-MRI parameters can be helpful in many aspects, including tumor grading, prediction of treatment response, likelihood of malignant transformation, discrimination between tumor recurrence and radiation necrosis, and differentiation between true early progression and pseudoprogression. This review aims to provide a conceptual overview of the underlying principles of DSC-MRI of the brain for clinical neuroradiologists, scientists, or students wishing to improve their understanding of the technical aspects, pitfalls, and controversies of DSC perfusion MRI of the brain. Future consensus on image acquisition parameters and postprocessing of DSC-MRI will most likely allow this technique to be evaluated and used in high-quality multicenter studies and ultimately help guide clinical care.


Subject(s)
Brain Neoplasms/diagnosis , Magnetic Resonance Imaging/methods , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Contrast Media , Disease Progression , Hemodynamics , Humans , Neoplasm Grading , Neoplasm Recurrence, Local/diagnosis
11.
BMC Med Genomics ; 7: 39, 2014 Jun 25.
Article in English | MEDLINE | ID: mdl-24962150

ABSTRACT

BACKGROUND: Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum at the base of the skull, resulting in significant neurologic morbidity. As CMI patients display a high degree of clinical variability and multiple mechanisms have been proposed for tonsillar herniation, it is hypothesized that this heterogeneous disorder is due to multiple genetic and environmental factors. The purpose of the present study was to gain a better understanding of what factors contribute to this heterogeneity by using an unsupervised statistical approach to define disease subtypes within a case-only pediatric population. METHODS: A collection of forty-four pediatric CMI patients were ascertained to identify disease subtypes using whole genome expression profiles generated from patient blood and dura mater tissue samples, and radiological data consisting of posterior fossa (PF) morphometrics. Sparse k-means clustering and an extension to accommodate multiple data sources were used to cluster patients into more homogeneous groups using biological and radiological data both individually and collectively. RESULTS: All clustering analyses resulted in the significant identification of patient classes, with the pure biological classes derived from patient blood and dura mater samples demonstrating the strongest evidence. Those patient classes were further characterized by identifying enriched biological pathways, as well as correlated cranial base morphological and clinical traits. CONCLUSIONS: Our results implicate several strong biological candidates warranting further investigation from the dura expression analysis and also identified a blood gene expression profile corresponding to a global down-regulation in protein synthesis.


Subject(s)
Arnold-Chiari Malformation/genetics , Gene Expression Profiling , Genome, Human/genetics , Skull/abnormalities , Child , Cluster Analysis , Female , Gene Expression Regulation , Humans , Magnetic Resonance Imaging , Male , Principal Component Analysis , Real-Time Polymerase Chain Reaction
12.
Ann Hum Genet ; 78(1): 1-12, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24359474

ABSTRACT

Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the base of the skull. Although cerebellar tonsillar herniation (CTH) is hypothesized to result from an underdeveloped posterior cranial fossa (PF), patients are frequently diagnosed by the extent of CTH without cranial morphometric assessment. We recently completed the largest CMI whole genome qualitative linkage screen to date. Despite an initial lack of statistical evidence, stratified analyses using clinical criteria to reduce heterogeneity resulted in a striking increase in evidence for linkage. The present study focused on the use of cranial base morphometrics to further dissect this heterogeneity and increase power to identify disease genes. We characterized the genetic contribution for a series of PF traits and evaluated the use of heritable, disease-relevant PF traits in ordered subset analysis (OSA). Consistent with a genetic hypothesis for CMI, much of the PF morphology was found to be heritable and multiple genomic regions were strongly implicated from OSA, including regions on Chromosomes 1 (LOD = 3.07, p = 3 × 10(-3) ) and 22 (LOD = 3.45, p = 6 × 10(-5) ) containing several candidates warranting further investigation. This study underscores the genetic heterogeneity of CMI and the utility of PF traits in CMI genetic studies.


Subject(s)
Arnold-Chiari Malformation/diagnosis , Arnold-Chiari Malformation/genetics , Cranial Fossa, Posterior/abnormalities , Endophenotypes , Quantitative Trait, Heritable , Adolescent , Adult , Child , Female , Genetic Linkage , Humans , Male , Middle Aged , Principal Component Analysis , Young Adult
13.
AJR Am J Roentgenol ; 201(5): W730-4, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24063388

ABSTRACT

OBJECTIVE: The purpose of this study was to measure the organ doses and estimate the effective dose for the standard brain perfusion CT protocol and erroneous protocols. MATERIALS AND METHODS: An anthropomorphic phantom with metal oxide semiconductor field effect transistor (MOSFET) detectors was scanned on a 64-MDCT scanner. Protocol 1 used a standard brain perfusion protocol with 80 kVp and fixed tube current of 200 mA. Protocol 2 used 120 kVp and fixed tube current of 200 mA. Protocol 3 used 120 kVp with automatic tube current modulation (noise index, 2.4; minimum, 100 mA; maximum, 520 mA). RESULTS: Compared with protocol 1, the effective dose was 2.8 times higher with protocol 2 and 7.8 times higher with protocol 3. For all protocols, the peak dose was highest in the skin, followed by the brain and calvarial marrow. Compared with protocol 1, the peak skin dose was 2.6 times higher with protocol 2 and 6.7 times higher with protocol 3. The peak skin dose for protocol 3 exceeded 3 Gy. The ocular lens received significant scatter radiation: 177 mGy for protocol 2 and 435 mGy for protocol 3, which were 4.6 and 11.3 times the dose for protocol 1, respectively. CONCLUSION: Compared with the standard protocol, erroneous protocols of increasing the tube potential from 80 kVp to 120 kVp will lead to a three- to fivefold increase in organ doses, and concurrent use of high peak kilovoltage with incorrectly programmed tube current modulation can increase dose to organs by 7- to 11-fold. Tube current modulation with a low noise index can lead to doses to the skin and ocular lens that are close to thresholds for tissue reactions.


Subject(s)
Brain/diagnostic imaging , Radiation Dosage , Radiometry/methods , Tomography, X-Ray Computed/methods , Humans , Phantoms, Imaging , Tomography, X-Ray Computed/instrumentation
14.
AJR Am J Roentgenol ; 201(3): W495-510, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23971482

ABSTRACT

OBJECTIVE: This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION: Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of per-fusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols.


Subject(s)
Central Nervous System Diseases/diagnosis , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Central Nervous System Diseases/pathology , Contrast Media , Humans , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods
15.
PLoS One ; 8(4): e61521, 2013.
Article in English | MEDLINE | ID: mdl-23620759

ABSTRACT

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.


Subject(s)
Arnold-Chiari Malformation/genetics , Genetic Association Studies , Genetic Linkage , Genetic Predisposition to Disease , Genome, Human/genetics , Klippel-Feil Syndrome/genetics , Chromosome Segregation/genetics , Female , Genotyping Techniques , Growth Differentiation Factor 3/genetics , Growth Differentiation Factor 6/genetics , Humans , Lod Score , Male , Molecular Sequence Data , Mutation, Missense/genetics , Pedigree , Sequence Analysis, DNA
17.
AJR Am J Roentgenol ; 200(1): 24-34, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23255738

ABSTRACT

OBJECTIVE: This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION: Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols.


Subject(s)
Brain Diseases/diagnosis , Brain/blood supply , Contrast Media , Magnetic Resonance Angiography/methods , Contrast Media/administration & dosage , Contrast Media/adverse effects , Gadolinium , Gadolinium DTPA/adverse effects , Humans , Injections, Intravenous , Magnetic Resonance Angiography/adverse effects , Organometallic Compounds/adverse effects
18.
Surg Neurol Int ; 3: 84, 2012.
Article in English | MEDLINE | ID: mdl-22937484

ABSTRACT

BACKGROUND: The purpose of this study is to retrospectively review our experience with stent-assisted embolization of patients with an acutely ruptured cerebral aneurysm. METHODS: Medical records and imaging were reviewed for 36 patients who underwent stent-assisted embolization of a ruptured cerebral aneurysm. RESULTS: Seventeen patients (47%) received a preprocedural loading dose of clopidogrel and five patients (14%) received an intraprocedural dose of clopidogrel. The remaining 14 patients (36%) were treated with antiplatelet therapy following the procedure. Six (17%) stent related intraprocedural thromboembolic complications were encountered; four of these resolved (one partial, three complete) following treatment with abciximab and/or heparin during the procedure. Five of the six thromboembolic events occurred in patients who were not pretreated with clopidogrel (P = 0.043). Two patients in this series (6%) had a permanent thrombotic complication resulting in mild hemiparesis in one patient, and hemianopsia in the second. No procedure related hemorrhagic complications occurred in any patient. One patient had a spontaneous parenchymal hemorrhage contralateral to the treated aneurysm discovered 10 days after treatment. Twenty-eight patients (78%) had a Glasgow Outcome Score of 4 or better at discharge. Seven of 21 patients (33%) with angiographic follow-up required further treatment of the coiled aneurysm. CONCLUSION: Stent-assisted coil embolization is an option for treatment of ruptured wide neck ruptured aneurysms and for salvage treatment during unassisted embolization of ruptured aneurysms but complications and retreatment rates are higher than for routine clipping or coiling of cerebral aneurysms. Pretreatment with clopidogrel appears effective in reducing thrombotic complications without significant increasing risk of hemorrhagic complications.

19.
Radiat Prot Dosimetry ; 150(1): 50-4, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21926088

ABSTRACT

The purpose of this study was to measure organ doses and the effective dose (ED) using a three-dimensional rotational X-ray (3D-RX) system and to determine the ED conversion factor from the dose area product (DAP) for skull, spine and biliary protocols. A commercial 3D-RX imaging system was used to simulate the protocols with the adult female anthropomorphic phantom. Twenty MOSFET detectors were used to measure the absorbed doses at various organ locations. The ED was calculated for each protocol and the corresponding DAP was obtained. The skin dose was the highest for all the protocols. The second highest organ doses were those of the brain for the skull, the intestine for the spine and the kidney for the biliary protocol. The ED was 0.4-0.9, 4.2-8.4 and 3.2-4.6 mSv, and the ED conversion factor was 0.06-0.09, 0.18-0.31 and 0.13-0.23 mSv Gy(-1) cm(-2) for each protocol, respectively. This data may be used to estimate the patient ED for those protocols in the 3D-RX.


Subject(s)
Imaging, Three-Dimensional , Radiation Dosage , Radiation Protection/methods , Tomography, X-Ray Computed , Viscera , Whole-Body Counting/methods , Adult , Algorithms , Computer Simulation , Female , Humans , Models, Biological , Phantoms, Imaging , Relative Biological Effectiveness , Rotation
20.
Neurosurgery ; 69(2): 369-75, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21499154

ABSTRACT

BACKGROUND: The Neuroform Stent has facilitated the endovascular treatment of wide-necked cerebral aneurysms. It is unknown which factors pose risks of thromboembolic events after stent placement. OBJECTIVE: This series is the largest single-center study reporting on the incidence of and factors influencing thromboembolic complications after Neuroform stent placement. METHODS: A total of 235 patients were treated with 274 Neuroform stents. The thromboembolic event rate was determined by imaging or clinical evidence of cerebrovascular accident within 90 days of stent placement; for patients with incomplete follow-up through chart review, telephone interviews were conducted. Analyses were performed to investigate patient factors that may be associated with stroke. RESULTS: Most aneurysms were unruptured; 30 patients (12.8%) presented with acute subarachnoid hemorrhage. Twelve patients of the 224 with follow-up (5.4%, 95% confidence interval: 2.4%-8.3%) demonstrated imaging or clinical evidence of a new thromboembolic event within 90 days of stent placement. There was a 3.1% thromboembolic rate for unruptured aneurysms and a 20% rate in patients with subarachnoid bleed. Hemorrhage was significantly associated with having a thromboembolic event (P = .002). There was a trend toward an increased thromboembolic event rate for patients with hypertension (P = .07). Larger stent caliber was significantly associated with a decreased thromboembolic event rate (P = .032). CONCLUSION: Our results suggest that the thromboembolic event rate associated with Neuroform stent use is low in unruptured aneurysms. In ruptured aneurysms, the complication rate is high, possibly partly related to restricted use of antiplatelet therapy. Stent size and hypertension may be associated with the risk of stroke, but additional studies are needed to confirm their significance.


Subject(s)
Endovascular Procedures/adverse effects , Intracranial Aneurysm/surgery , Postoperative Complications/epidemiology , Stents/adverse effects , Thromboembolism/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Aneurysm, Ruptured/surgery , Child , Female , Humans , Incidence , Intracranial Aneurysm/pathology , Male , Middle Aged , Postoperative Complications/etiology , Thromboembolism/etiology , Young Adult
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