Breath-Hold Induced Cerebrovascular Reactivity Measurements Using Optimized Pseudocontinuous Arterial Spin Labeling.

A pseudocontinuous arterial spin labeling (PCASL) sequence combined with background suppression and single-shot accelerated 3D RARE stack-of-spirals was used to evaluate cerebrovascular reactivity (CVR) induced by breath-holding (BH) in ten healthy volunteers. Four different models designed using the measured change in PETCO2 induced by BH were compared, for CVR quantification. The objective of this comparison was to understand which regressor offered a better physiological model to characterize the cerebral blood flow response under BH. The BH task started with free breathing of 42 s, followed by interleaved end-expiration BHs of 21 s, for ten cycles. The total scan time was 12 min and 20 s. The accelerated readout allowed the acquisition of PCASL data with better temporal resolution than previously used, without compromising the post-labeling delay. Elevated CBF was observed in most cerebral regions under hypercapnia, which was delayed with respect to the BH challenge. Significant statistical differences in CVR were obtained between the different models in GM (p < 0.0001), with ramp models yielding higher values than boxcar models and between the two tissues, GM and WM, with higher values in GM, in all the models (p < 0.0001). The adjustment of the ramp amplitude during each BH cycle did not improve the results compared with a ramp model with a constant amplitude equal to the mean PETCO2 change during the experiment.

Cochlear-Internal Canal and Cochlear-Facial Dehiscence: A Novel Entity.

Different types of otic capsule dehiscence restricted to the cochlea have been described. Here we describe the case of a patient with a cochlear-internal auditory canal dehiscence associated with a cochlear-facial dehiscence not reported before. A 53-year-old patient with severe to profound sensorineural hearing loss due to bilateral Meniere's disease underwent a cochlear implant surgery on the right ear. Preoperative brain magnetic resonance imaging findings were reported to be normal; during surgery, a cerebrospinal fluid gusher occurred at the time of round window opening. Postoperative computed tomography imaging showed a bony dehiscence at two levels of the otic capsule.

DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report.

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive glial brain tumors that primarily affect children, for which there is no curative treatment. Median overall survival is only one year. Currently, the scientific focus is on expanding the knowledge base of the molecular biology of DIPG, and identifying effective therapies. Oncolytic adenovirus DNX-2401 is a replication-competent, genetically modified virus capable of infecting and killing glioma cells, and stimulating an anti-tumor immune response. Clinical trials evaluating intratumoral DNX-2401 in adults with recurrent glioblastoma have demonstrated that the virus has a favorable safety profile and can prolong survival. Subsequently, these results have encouraged the transition of this biologically active therapy from adults into the pediatric population. To this aim, we have designed a clinical Phase I trial for newly diagnosed pediatric DIPG to investigate the feasibility, safety, and preliminary efficacy of delivering DNX-2401 into tumors within the pons following biopsy. This case report presents a pediatric patient enrolled in this ongoing Phase I trial for children and adolescents with newly diagnosed DIPG. The case involves an 8-year-old female patient with radiologically diagnosed DIPG who underwent stereotactic tumor biopsy immediately followed by intratumoral DNX-2401 in the same biopsy track. Because there were no safety concerns or new neurological deficits, the patient was discharged 3 days after the procedures. To our knowledge, this is the first report of intratumoral DNX-2401 for a patient with DIPG in a clinical trial. We plan to demonstrate that intratumoral delivery of an oncolytic virus following tumor biopsy for pediatric patients with DIPG is a novel and feasible approach and that DNX-2401 represents an innovative treatment for the disease.

Development of a DIPG Orthotopic Model in Mice Using an Implantable Guide-Screw System.

OBJECTIVE: In this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG) model based in the implantation of a guide-screw system. METHODS: It consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies. RESULTS: The guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model. CONCLUSION: Here we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons.

Intracranial extramedullary hematopoiesis associated with multiple myeloma.

A 77-year-old woman with multiple myeloma for 5 years presented with obtundation, drowsiness, and disorientation over 15 days. Complete blood count revealed thrombocytopenia (25,000/µL). A brain CT disclosed multiple extraaxial hyperdense foci without bone destruction. Differential diagnosis included tumors (meningiomas, leukemia), subdural hematomas, and intracranial hemorrhages; the lesion's multiplicity and morphology were consistent with intracranial extramedullary hematopoiesis (IEH) (figure). Despite platelet transfusions, she died 2 days later of alveolar hemorrhage. Autopsy confirmed IEH and excluded erythropoiesis, reported in subdural hematomas. The formation of blood cells outside the bone marrow is usually related to anemia or lymphoproliferative disorders and is uncommon in multiple myeloma.(1) IEH can cause seizures, hydrocephalus, or cognitive changes.(2.)

Functional bold MRI: advantages of the 3 T vs. the 1.5 T.

We quantitatively evaluate the benefits of a higher field strength for functional brain MRI (fMRI) based on the blood oxygenation level-dependent contrast. The 3-T fMRI shows a higher sensitivity for the motor and somatosensory stimulation and more specific localization in the grey substance. The 3-T fMRI detects additional areas of activation with the motor paradigm.

Preoperative planning of DIEP and SGAP flaps: preliminary experience with magnetic resonance angiography using 3-tesla equipment and blood-pool contrast medium.

BACKGROUND: Autologous breast reconstruction techniques can be used to create a breast, in particular the superior gluteal artery perforator (SGAP) and deep inferior epigastric artery perforator (DIEP) flaps. Preoperative imaging is an essential planning tool in mapping the location and size of perforator vessels. The aim of this report is to show the usefulness of angio-MR technique for preoperative planning of DIEP and SGAP flaps. Initial experience, surgical findings correlation and imaging findings will be described. METHODS: From February 2007 to September 2007, ten consecutive women considered for breast reconstruction with DIEP (eight patients) and SGAP flaps (two patients) after previous mastectomy for breast cancer were studied. After written informed consent was obtained, a preoperative angio-MR using 3-Tesla equipment and blood-pool contrast medium was performed to localize and evaluate the main perforator vessels in each patient and procedure. RESULTS: Angio-MR showed all the main perforator vessels later observed during the surgical procedure with a very good location concordance, but missed one main perforator vessels in each of two patients. In all patients undergoing SGAP flaps, an accurate identification of the main perforator vessels was achieved. Angio-MR clearly showed the intramuscular course of the perforator vessels for DIEP and SGAP flaps. Exact correlation between angio-MR and surgical findings was observed. CONCLUSIONS: The use of angio-MR for preoperative perforator flaps evaluation yielded promising results and would allow not only to locate perforator vessels but also to globally assess presurgical planning of perforator flaps in a noninvasive, radiation and toxicity-free way.