Feasibility of percutaneous dural sac puncture via a posterior trans-sacral foraminal conduit approach: a CT morphometric analysis.

We assess the theoretical feasibility of percutaneous posterior sacral foramen (pSF) needle puncture of the sacral dural sac (DS) by studying the three-dimensional imaging anatomy of pSFs relative to the sacral canal (SC). On CT images of 40 healthy subjects, we retrospectively studied sacral alae passageways from SC to pSFs in all three planes to determine if an imaginary spinal needle could theoretically traverse S1 or S2 pSFs in a straight path toward DS. If not straight, we measured multiplane angulations and morphometrics of this route. We found no straight connections between S1 or S2 pSFs and SC. Instead, there were bilateral spatially complex dorsoventral M-shaped "foraminal conduits" (FCs; common, ventral, and dorsal) from SC to anterior SFs and pSFs that would prevent percutaneous straight needle puncture of the DS. This detailed knowledge of the sacral FCs will be useful for accurate imaging interpretation and interventional procedures on the sacrum.

Caudolenticular gray bridges of the brain: A magnetic resonance imaging study.

The caudolenticular (or transcapsular) gray bridges (CLGBs) connect the caudate nucleus (CN) and putamen across the internal capsule. The CLGBs function as the main efferent terminus from premotor and supplementary motor area cortex to the basal ganglia (BG). We conjectured if inherent variations in numbers and sizes of CLGBs could contribute to abnormal cortical-subcortical connectivity in Parkinson's disease (PD), a neurodegenerative disorder featuring a hindrance of BG processing. However, there are no literature accounts of normative anatomy and morphometry of CLGBs. We therefore retrospectively analyzed axial and coronal 3T fast spoiled gradient-echo magnetic resonance images (MRIs) of 34 healthy individuals for bilateral CLGBs symmetry, their numbers, dimensions of thickest and longest bridge, and axial surface areas of CN head and putamen. We calculated Evans' index (EI) to account for any brain atrophy. We statistically tested associations between sex or age and measured dependent variables, and linear correlations between all measured variables (significance at p < 0.05). Study subjects were F:M = 23:11 with mean age 49.9 years. All EI's were normal (<0.3). All but three CLGBs were bilaterally symmetrical with a mean 7.4 CLGBs per side. Mean CLGBs thickness and lengths were 1.0 and 4.6 mm, respectively; CN head and putamen areas were 205 and 382.0 mm2 , respectively. Females had thicker CLGBs (p = 0.02) but we found no significant interactions between sex or age and measured dependent variables, and no correlations between CN head or putamen areas and CLGBs dimensions. These normative MRI dimensions of the CLGBs will help guide future studies on the possible role of CLGBs morphometry in PD predisposition.

Atavistic and vestigial anatomical structures in the head, neck, and spine: an overview.

Organisms may retain nonfunctional anatomical features as a consequence of evolutionary natural selection. Resultant atavistic and vestigial anatomical structures have long been a source of perplexity. Atavism is when an ancestral trait reappears after loss through an evolutionary change in previous generations, whereas vestigial structures are remnants that are largely or entirely functionless relative to their original roles. While physicians are cognizant of their existence, atavistic and vestigial structures are rarely emphasized in anatomical curricula and can, therefore, be puzzling when discovered incidentally. In addition, the literature is replete with examples of the terms atavistic and vestigial being used interchangeably without careful distinction between them. We provide an overview of important atavistic and vestigial structures in the head, neck, and spine that can serve as a reference for anatomists and clinical neuroscientists. We review the literature on atavistic and vestigial anatomical structures of the head, neck, and spine that may be encountered in clinical practice. We define atavistic and vestigial structures and employ these definitions consistently when classifying anatomical structures. Pertinent anatomical structures are numerous and include human tails, plica semilunaris, the vomeronasal organ, levator claviculae, and external ear muscles, to name a few. Atavistic and vestigial structures are found throughout the head, neck, and spine. Some, such as human tails and branchial cysts may be clinically symptomatic. Literature reports indicate that their prevalence varies across populations. Knowledge of atavistic and vestigial anatomical structures can inform diagnoses, prevent misrecognition of variation for pathology, and guide clinical interventions.

Feasibility of intrathecal therapeutic injections in spinal muscular atrophy patients via a percutaneous transsacral hiatus route: An initial neuroimaging morphometric study.

INTRODUCTION/AIMS: Standard fluoroscopic lumbar puncture (LP) can be impossible in patients with severe spinal deformities from spinal muscular atrophy (SMA) who require intrathecal nusinersen therapy. There usually exists a straight trajectory in the lower sacral canal (SC) that could allow image-guided percutaneous transsacral hiatus puncture of the lumbosacral dural sac. In this study we determine whether sacra are comparatively straighter in SMA patients (SMAps) vs healthy controls (HCs), which may facilitate unhindered transsacral hiatus spinal needle insertion for intrathecal nusinersen therapy. METHODS: We retrospectively analyzed lumbosacral spine computed tomograms (CTs) or CT-myelogram images of 38 SMAps and age- and sex-matched HCs. We digitally measured ventrodorsal sacral curvatures, SC surface areas, dural sac termination levels, and distances from sacral hiatus to the most caudad aspects of dural sacs ("needle distance"). RESULTS: Mean ages of HCs and SMAps were 32.7 and 31.7 years, respectively, with dural sacs terminating at similar levels. Mean values for morphometrics were: (a) midsagittal SC surface area for HCs = 701.2 mm2 , and for SMAps = 601.5 mm2 (not statistically significant [ns]); (b) using a "line method," sacral curvature for HCs = 61.9°, and SMAp = 35.7° (P = .0009), and was similar when using an "angle summation method"; (c) width of sacral hiatus for HCs = 14.9 mm, and SMAps = 15.0 mm (ns); and (d) "needle distance" for HCs = 54.7 mm, and SMAps = 49.9 mm (ns). DISCUSSION: SMAps have significantly straighter sacra compared with HCs, which theoretically renders them more amenable to percutaneous transsacral hiatus puncture of the dural sac.

A New Nrf2 Inhibitor Enhances Chemotherapeutic Effects in Glioblastoma Cells Carrying p53 Mutations.

TP53 tumor suppressor gene is a commonly mutated gene in cancer. p53 mediated senescence is critical in preventing oncogenesis in normal cells. Since p53 is a transcription factor, mutations in its DNA binding domain result in the functional loss of p53-mediated cellular pathways. Similarly, nuclear factor erythroid 2-related factor 2 (Nrf2) is another transcription factor that maintains cellular homeostasis by regulating redox and detoxification mechanisms. In glioblastoma (GBM), Nrf2-mediated antioxidant activity is upregulated while p53-mediated senescence is lost, both rendering GBM cells resistant to treatment. To address this, we identified novel Nrf2 inhibitors from bioactive compounds using a molecular imaging biosensor-based screening approach. We further evaluated the identified compounds for their in vitro and in vivo chemotherapy enhancement capabilities in GBM cells carrying different p53 mutations. We thus identified an Nrf2 inhibitor that is effective in GBM cells carrying the p53 (R175H) mutation, a frequent clinically observed hotspot structural mutation responsible for chemotherapeutic resistance in GBM. Combining this drug with low-dose chemotherapies can potentially reduce their toxicity and increase their efficacy by transiently suppressing Nrf2-mediated detoxification function in GBM cells carrying this important p53 missense mutation.

Anatomy of the Orbit.

Each orbit is a complex structure housing the globe, multiple cranial nerves, muscles, vascular structures, which support the visual sense. Many of these structures have been delineated in careful detail by anatomists but remain beyond the resolution of conventional imaging techniques. With the advances of higher resolution MR, surface coil usage, and thinner section computed tomographic images, the ability to resolve these small structures continues to improve, allowing radiologists to provide more detailed anatomic descriptions for preoperative and pretreatment planning.

Oral Cavity and Salivary Glands Anatomy.

Knowledge of anatomy is essential to the understanding of disease and conditions of the oral cavity and salivary glands. This article is intended to serve as an overview of the oral cavity, its subsites, and that of the neighboring salivary glands. The authors cover the anatomy of the lips, tongue, floor of mouth, hard palate, teeth, various mucosal areas, and salivary ducts. When appropriate, radiological imaging along with figures serves as a companion to highlight the clinical relevance and practical applications of specific anatomic locations.

Root of the Neck and Extracranial Vessel Anatomy.

The root of the neck is the junctional anatomic structure between the thoracic inlet, the axilla, and the lower neck. The detailed radiological anatomy of this critical area is discussed in this review.

Thoracic and Lumbosacral Spine Anatomy.

We review anatomy of the thoracic, lumbar, and sacral spine. Knowledge of normal anatomy is vital when reviewing imaging of the spine because it allows for the detection of abnormal findings. We emphasize the normal appearance of the thoracic and lumbosacral spine on imaging, focusing on the most common imaging techniques of computed tomography and magnetic resonance imaging, as well as highlighting a few less common and emerging imaging techniques that can evaluate the spine.

Anatomy of the Spinal Cord, Coverings, and Nerves.

The spinal cord is an elegant structure that serves as a conduit for the transfer of information between the brain and the peripheral nervous system. To enable the reader to understand its complex microstructural anatomy, we have created a detailed yet approachable anatomic reference for clinicians. We review gross and structural features of the spinal cord, its coverings, and nerves while also discussing spinal cord development, microscopic organization, and common anatomic variants. We detail how this anatomy appears on current neuroimaging techniques, with special attention to MR imaging.

Inhaled Gold Nano-star Carriers for Targeted Delivery of Triple Suicide Gene Therapy and Therapeutic MicroRNAs to Lung Metastases: Development and Validation in a Small Animal Model.

Pulmonary metastases pose significant treatment challenges for many cancers, including triple-negative breast cancer (TNBC). We developed and tested a novel suicide gene and therapeutic microRNAs (miRs) combination therapy against lung metastases in vivo in mouse models after intranasal delivery using nontoxic gold nanoparticles (AuNPs) formulated to carry these molecular therapeutics. We used AuNPs coated with chitosan-ß-cyclodextrin (CS-CD) and functionalized with a urokinase plasminogen activator (uPA) peptide to carry triple cancer suicide genes (thymidine kinase-p53-nitroreductase: TK-p53-NTR) plus therapeutic miRNAs (antimiR-21, antimiR-10b and miR-100). We synthesized three AuNPs: 20nm nanodots (AuND), and 20nm or 50nm nanostars (AuNS), then surface coated these with CS-CD using a microfluidic-optimized method. We sequentially coated the resulting positively charged AuNP-CS-CD core with synthetic miRNAs followed by TK-p53-NTR via electrostatic interactions, and added uPA peptide through CD-adamantane host-guest chemistry. A comparison of transfection efficiencies for different AuNPs showed that the 50nm AuNS allowed ∼4.16-fold higher gene transfection than other NPs. The intranasal delivery of uPA-AuNS-TK-p53-NTR-microRNAs NPs (pAuNS@TK-p53-NTR-miRs) in mice predominantly accumulated in lungs and facilitated ganciclovir and CB1954 prodrug-mediated gene therapy against TNBC lung metastases. This new nanosystem may serve as an adaptable-across-cancer-type, facile, and clinically scalable platform to allow future inhalational suicide gene-miR combination therapy for patients harboring pulmonary metastases.

Anatomy of the Calvaria and Skull Base.

A thorough understanding of the skull anatomy is of key importance to radiologists as well as specialist physicians and surgeons. We describe the anatomy of the neurocranium comprising calvaria (the skull vault) and the skull base and discuss the most common and clinically relevant anatomic variants.

Anatomy of the Cerebral Cortex, Lobes, and Cerebellum.

Strong foundational knowledge of the anatomy of the cerebral cortex, lobes, and cerebellum is key to guide the search for potential lesions based on clinical presentation and known focal neurologic deficits. This article provides an introduction and overview of cerebral cortical anatomy, including the key sulci that divide the 4 lobes of the cerebral cortex, as well as the major gyral and sulcal landmarks within each lobe. The organization of the cerebellum and its major anatomic constituents are also described. Commonly encountered anatomic variants and asymmetries in cerebral cortical anatomy are presented and discussed.

Anatomy of Intracranial Veins.

The cerebral venous system is complex and sophisticated and serves various major functions toward maintaining brain homeostasis. Cerebral veins contain about 70% of cerebral blood volume, have thin walls, are valveless, and cross seamlessly white matter, ependymal, cisternal, arachnoid, and dural boundaries to eventually drain cerebral blood either into dural sinuses or deep cerebral veins. Although numerous variations in the cerebral venous anatomic arrangement may be encountered, the overall configuration is relatively predictable and landmarks relatively well defined. A reasonable understanding of cerebral vascular embryology is helpful to appreciate normal anatomy and variations that have clinical relevance. Increasing interest in transvascular therapy, particularly transvenous endovascular intervention provides justification for practitioners in the neurosciences to acquire at least a basic understanding of the cerebral venous system.