Cytotechnologist performance for screening microfollicular atypia in indeterminate thyroid fine-needle aspirates.

INTRODUCTION: We previously identified a high level of accuracy among our cytotechnologists (CTs) for identifying nuclear atypia in thyroid fine-needle aspiration (FNA) specimens. Herewith, we present our CT performance at screening for microfollicular atypia. METHODS: 8,814 thyroid FNA specimens were identified in our archives, all screened by 1 of 11 CTs and signed out by a cytopathologist. A subsample of cases was categorized either as atypia of uncertain significance (AUS) with microfollicular proliferation (AUS-F) or suspicious for a follicular neoplasm (SFN). RESULTS: The agreement rate was low between CTs and cytopathologists for SFN and AUS-F. Only 55.8% of SFN screening diagnoses were upheld; 27.9% were downgraded to AUS, 10.4% were downgraded to benign, and 5% were upgraded. Of AUS-F screening diagnoses, 35.5% were upheld, 33.7% were downgraded to benign, and 20.2% were upgraded to SFN. Among all cases, two-step discrepancies were uncommon. CONCLUSION: Most disagreements were one-category discrepancies between AUS-F and SFN. The evaluation of microfollicular atypia is challenging given that certain follicular lesions cannot be definitively diagnosed on cytology, a high level of subjectivity is involved in the interpretation of such lesions, and the presence of nuclear or Hurthle cell atypia may complicate the diagnosis.

Cytotechnologist performance for detecting nuclear atypia in indeterminate thyroid fine needle aspirates.

INTRODUCTION: The thyroid gland is arguably the fastest growing anatomic site for fine needle aspiration (FNA). With the increase of thyroid cases, a reevaluation of cytotechnologist screening quality metrics in terms of thyroid FNA is called for. We present our institutional cytotechnologist performance at screening for nuclear atypia by applying established quality metrics. MATERIALS AND METHODS: Information on 8,814 consecutive thyroid cytopathology cases over a 10-year period was retrieved from computerized records. A subsample of cases categorized either as atypia of uncertain significance with nuclear atypia or suspicious for malignancy with features suspicious for papillary thyroid carcinoma. The cytotechnologist and cytopathologist diagnoses were compared using step discrepancies and Δ-ratios. RESULTS: Overall discrepancy between the cytotechnologist and cytopathologist diagnoses existed in <10% of all thyroid cases. One-category discrepancies were the most common (7.8%), while two-category discrepancies were rare (0.5%). The one-category discrepancy rate correlated with cytotechnologist experience. One-category under calls were twice as common as over calls (5.3 vs. 2.5%, p < 0.0001). CONCLUSIONS: We identified a high level of quality in the screening for nuclear atypia in thyroid FNA. The one-category discrepancy rate is suited to tracking individual cytotechnologist performance, identifies outliers and appears to correlate with cytotechnologist experience.

TP-RT domain interactions of duck hepatitis B virus reverse transcriptase in cis and in trans during protein-primed initiation of DNA synthesis in vitro.

The hepadnavirus reverse transcriptase (RT) has the unique ability to initiate viral DNA synthesis using RT itself as a protein primer. Protein priming requires complex interactions between the N-terminal TP (terminal protein) domain, where the primer (a specific Y residue) resides, and the central RT domain, which harbors the polymerase active site. While it normally utilizes the cis-linked TP to prime DNA synthesis (cis-priming), we found that the duck hepatitis B virus (DHBV) RT domain, in the context of the full-length RT protein or a mini-RT construct containing only truncated TP and RT domains, could additionally use a separate TP or RT domain in trans as a primer (trans-priming). trans interaction could also be demonstrated by the inhibitory effect (trans-inhibition) on cis-priming by TP and RT domain sequences provided in trans. Protein priming was further shown to induce RT conformational changes that resulted in TP-RT domain dissociation, altered priming site selection, and a gain of sensitivity to a pyrophosphate analog inhibitor. trans-priming, trans-inhibition, and trans-complementation, which requires separate TP and RT domains to reconstitute a functional RT protein, were employed to define the sequences in the TP and RT domains that could mediate physical or functional inter- and intradomain interactions. These results provide new insights into TP-RT domain interactions and conformational dynamics during protein priming and suggest novel means to inhibit protein priming by targeting these interactions and the associated conformational transitions.

Cyclin-dependent kinase 2 phosphorylates s/t-p sites in the hepadnavirus core protein C-terminal domain and is incorporated into viral capsids.

Phosphorylation of the hepadnavirus core protein C-terminal domain (CTD) is important for viral RNA packaging, reverse transcription, and subcellular localization. Hepadnavirus capsids also package a cellular kinase. The identity of the host kinase that phosphorylates the core CTD or gets packaged remains to be resolved. In particular, both the human hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) core CTDs harbor several conserved serine/threonine-proline (S/T-P) sites whose phosphorylation state is known to regulate CTD functions. We report here that the endogenous kinase in the HBV capsids was blocked by chemical inhibitors of the cyclin-dependent kinases (CDKs), in particular, CDK2 inhibitors. The kinase phosphorylated the HBV CTD at the serine-proline (S-P) sites. Furthermore, we were able to detect CDK2 in purified HBV capsids by immunoblotting. Purified CDK2 phosphorylated the S/T-P sites of the HBV and DHBV CTD in vitro. Inhibitors of CDKs, of CDK2 in particular, decreased both HBV and DHBV CTD phosphorylation in vivo. Moreover, CDK2 inhibitors blocked DHBV CTD phosphorylation, specifically at the S/T-P sites, in a mammalian cell lysate. These results indicate that cellular CDK2 phosphorylates the functionally critical S/T-P sites of the hepadnavirus core CTD and is incorporated into viral capsids.

Secretion of genome-free hepatitis B virus--single strand blocking model for virion morphogenesis of para-retrovirus.

As a para-retrovirus, hepatitis B virus (HBV) is an enveloped virus with a double-stranded (DS) DNA genome that is replicated by reverse transcription of an RNA intermediate, the pregenomic RNA or pgRNA. HBV assembly begins with the formation of an "immature" nucleocapsid (NC) incorporating pgRNA, which is converted via reverse transcription within the maturing NC to the DS DNA genome. Only the mature, DS DNA-containing NCs are enveloped and secreted as virions whereas immature NCs containing RNA or single-stranded (SS) DNA are not enveloped. The current model for selective virion morphogenesis postulates that accumulation of DS DNA within the NC induces a "maturation signal" that, in turn, triggers its envelopment and secretion. However, we have found, by careful quantification of viral DNA and NCs in HBV virions secreted in vitro and in vivo, that the vast majority of HBV virions (over 90%) contained no DNA at all, indicating that NCs with no genome were enveloped and secreted as empty virions (i.e., enveloped NCs with no DNA). Furthermore, viral mutants bearing mutations precluding any DNA synthesis secreted exclusively empty virions. Thus, viral DNA synthesis is not required for HBV virion morphogenesis. On the other hand, NCs containing RNA or SS DNA were excluded from virion formation. The secretion of DS DNA-containing as well as empty virions on one hand, and the lack of secretion of virions containing single-stranded (SS) DNA or RNA on the other, prompted us to propose an alternative, "Single Strand Blocking" model to explain selective HBV morphogenesis whereby SS nucleic acid within the NC negatively regulates NC envelopment, which is relieved upon second strand DNA synthesis.

Inhibitors of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] identified by in silico molecular docking.

AAC(6')-Ib is an important aminoglycoside resistance enzyme to target with enzymatic inhibitors. An in silico screening approach was used to identify potential inhibitors from the ChemBridge library. Several compounds were identified, of which two of them, 4-[(2-{[1-(3-methylphenyl)-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene]methyl}phenoxy)methyl]benzoic acid and 2-{5-[(4,6-dioxo-1,3-diphenyl-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid, showed micromolar activity in inhibiting acetylation of kanamycin A. These compounds are predicted to bind the aminoglycoside binding site of AAC(6')-Ib and exhibited competitive inhibition against kanamycin A.

Achromobacter xylosoxidans: an emerging pathogen carrying different elements involved in horizontal genetic transfer.

In the last few years, numerous cases of multidrug-resistant Achromobacter xylosoxidans infections have been documented in immunocompromised and cystic fibrosis patients. To gain insights into the molecular mechanisms and mobile elements related to multidrug resistance in this bacterium, we studied 24 non-epidemiological A. xylosoxidans clinical isolates from Argentina. Specific primers for plasmids, transposons, insertion sequences, bla(ampC), intI1, and intI2 genes were used in PCR reactions. The obtained results showed the presence of wide host range IncP plasmids in ten isolates and a high dispersion of class 1 integrons (n = 10) and class 2 integrons (n = 3). Four arrays in the variable region (vr) of class 1 integrons were identified carrying different gene cassettes as the aminoglycoside resistance aac(6')-Ib and aadA1, the trimethoprim resistance dfrA1 and dfrA16, and the ß-lactamase bla(OXA-2). In only one of the class 2 integrons, a vr was amplified that includes sat2-aadA1. The bla(ampC) gene was found in all isolates, confirming its ubiquitous nature. Our results show that A. xylosoxidans clinical isolates contain a rich variety of genetic elements commonly associated with resistance genes and their dissemination. This supports the hypothesis that A. xylosoxidans is becoming a reservoir of horizontal genetic transfer elements commonly involved in spreading antibiotic resistance.

The Value of Second-Opinion Consultation in Nongynecologic Cytopathology.

OBJECTIVES: The value of consultation in pathology has been well documented in surgical pathology, but there are few comprehensive studies of consultation cases in cytopathology. Here we report our experience with cytopathology consultation cases at a large academic center. METHODS: A review of consultation cases at our institution was performed by searching our laboratory information system. The contributing institution's diagnosis was compared with that rendered by the reviewing cytopathologist to assess major and/or minor diagnostic discrepancies. RESULTS: In total, 928 cases were reviewed with the following distribution: fine-needle aspiration (FNA, 79.4%), exfoliative nongynecologic cytology (18.3%), and cases with both FNA and nongynecologic cytology (2.3%). There were 379 (40.8%) true consults and 549 (59.2%) confirming consults. A total of 586 (63.1%) cases were in agreement with the outside pathologist, 78 (8.4%) cases had major discrepancies, and 264 (28.4%) cases had minor discrepancies. Major discrepancies were most common for pancreas (38.5%), lymph node (11.5%), and soft tissue sites (9.0%). CONCLUSIONS: Of the cases, 8.4% had major diagnostic discrepancies between the original diagnosis and the consultation diagnosis, which is consistent with reported values in surgical pathology consultation studies. The findings support the importance of second-opinion consultation in cytopathology to guide patient care.

Transcriptional control of subtype switching ensures adaptation and growth of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a heterogeneous disease comprised of a basal-like subtype with mesenchymal gene signatures, undifferentiated histopathology and worse prognosis compared to the classical subtype. Despite their prognostic and therapeutic value, the key drivers that establish and control subtype identity remain unknown. Here, we demonstrate that PDA subtypes are not permanently encoded, and identify the GLI2 transcription factor as a master regulator of subtype inter-conversion. GLI2 is elevated in basal-like PDA lines and patient specimens, and forced GLI2 activation is sufficient to convert classical PDA cells to basal-like. Mechanistically, GLI2 upregulates expression of the pro-tumorigenic secreted protein, Osteopontin (OPN), which is especially critical for metastatic growth in vivo and adaptation to oncogenic KRAS ablation. Accordingly, elevated GLI2 and OPN levels predict shortened overall survival of PDA patients. Thus, the GLI2-OPN circuit is a driver of PDA cell plasticity that establishes and maintains an aggressive variant of this disease.

TP53 Status as a Determinant of Pro- vs Anti-Tumorigenic Effects of Estrogen Receptor-Beta in Breast Cancer.

BACKGROUND: Anti-tumorigenic vs pro-tumorigenic roles of estrogen receptor-beta (ESR2) in breast cancer remain unsettled. We investigated the potential of TP53 status to be a determinant of the bi-faceted role of ESR2 and associated therapeutic implications for triple negative breast cancer (TNBC). METHODS: ESR2-TP53 interaction was analyzed with multiple assays including the in situ proximity ligation assay. Transcriptional effects on TP53-target genes and cell proliferation in response to knocking down or overexpressing ESR2 were determined. Patient survival according to ESR2 expression levels and TP53 mutation status was analyzed in the basal-like TNBC subgroup in the Molecular Taxonomy of Breast Cancer International Consortium (n = 308) and Roswell Park Comprehensive Cancer Center (n = 46) patient cohorts by univariate Cox regression and log-rank test. All statistical tests are two-sided. RESULTS: ESR2 interaction with wild-type and mutant TP53 caused pro-proliferative and anti-proliferative effects, respectively. Depleting ESR2 in cells expressing wild-type TP53 resulted in increased expression of TP53-target genes CDKN1A (control group mean [SD] = 1 [0.13] vs ESR2 depletion group mean [SD] = 2.08 [0.24], P = .003) and BBC3 (control group mean [SD] = 1 [0.06] vs ESR2 depleted group mean [SD] = 1.92 [0.25], P = .003); however, expression of CDKN1A (control group mean [SD] = 1 [0.21] vs ESR2 depleted group mean [SD] = 0.56 [0.12], P = .02) and BBC3 (control group mean [SD] = 1 [0.03] vs ESR2 depleted group mean [SD] = 0.55 [0.09], P = .008) was decreased in cells expressing mutant TP53. Overexpressing ESR2 had opposite effects. Tamoxifen increased ESR2-mutant TP53 interaction, leading to reactivation of TP73 and apoptosis. High levels of ESR2 expression in mutant TP53-expressing basal-like tumors is associated with better prognosis (Molecular Taxonomy of Breast Cancer International Consortium cohort: log-rank P = .001; hazard ratio = 0.26, 95% confidence interval = 0.08 to 0.84, univariate Cox P = .02). CONCLUSIONS: TP53 status is a determinant of the functional duality of ESR2. Our study suggests that ESR2-mutant TP53 combination prognosticates survival in TNBC revealing a novel strategy to stratify TNBC for therapeutic intervention potentially by repurposing tamoxifen.

Activity of a novel antimicrobial peptide against Pseudomonas aeruginosa biofilms.

With the increasing recognition of biofilms in human disease, the development of novel antimicrobial therapies is of critical importance. For example, in patients with cystic fibrosis (CF), the acquisition of host-adapted, chronic Pseudomonas aeruginosa infection is associated with a decline in lung function and increased mortality. Our objective was to test the in vitro efficacy of a membrane-active antimicrobial peptide we designed, termed 6K-F17 (sequence: KKKKKK-AAFAAWAAFAA-NH2), against multidrug resistant P. aeruginosa biofilms. This peptide displays high antimicrobial activity against a range of pathogenic bacteria, yet is non-hemolytic to human erythrocytes and non-toxic to human bronchial epithelial cells. In the present work, P. aeruginosa strain PAO1, and four multidrug resistant (MDR) isolates from chronically infected CF individuals, were grown as 48-hour biofilms in a static biofilm slide chamber model. These biofilms were then exposed to varying concentrations of 6K-F17 alone, or in the presence of tobramycin, prior to confocal imaging. Biofilm biovolume and viability were assessed. 6K-F17 was able to kill biofilms - even in the presence of sputum - and greatly reduce biofilm biovolume in PAO1 and MDR isolates. Strikingly, when used in conjunction with tobramycin, low doses of 6K-F17 significantly potentiated tobramycin killing, leading to biofilm destruction.

Adherence in young children with asthma.

PURPOSE OF REVIEW: To discuss the unique challenges of managing asthma in young children and to review the literature over the past year with regard to regimen adherence in this relatively understudied population. RECENT FINDINGS: Young children and their families face unique challenges in dealing with asthma and these have the potential to affect regimen adherence. They include the time and effort required by asthma-management activities (e.g. nebulizer use), dependency on parents for asthma care, and the limited ability of children to communicate about their symptoms. Five published studies were found for the past year. They covered three areas: adherence assessment (e.g. electronic monitoring versus diary cards), device impact on adherence (e.g. influence of the novelty of medication-delivery device), and adherence interventions (e.g. parental education regarding symptoms). SUMMARY: Research suggests that several components need to be considered when designing interventions to improve adherence for young children with asthma: to consider the strain in the caregiver role when developing the treatment regimen, to provide devices that parents and children can use, to monitor adherence with electronic monitoring, and to address parents' concerns and perceptions about treating prodromal symptoms of an asthma exacerbation. Because many parents are hesitant to treat cough symptoms, an additional training component may need to be added to address this concern.

Social perceptions and preferences of youth with asthma.

Peers are a primary source of psychosocial support in youth. Chronic disease such as asthma can make youth feel different and impinge on their adherence to treatment. We investigated factors that make the asthmatic adolescent feel different from peers, and explore their willingness to belong to a peer social-group such as an asthma club. Sixty-six youth (ages 8-18 years) with asthma completed an anonymous questionnaire that included both multiple-choice and open-ended questions designed to explore the feelings of the respondents. Almost one-third of our sample reported negative feelings regarding their asthma. Nearly 27% reported that their diagnosis made them feel different from their healthy peers, while over 25% admitted feeling uncomfortable using their inhaler in front of their friends. Almost one-half of adolescents felt restricted or excluded from school activities, athletics, or social clubs. While most respondents (93.9%)

Combined Treatment with Epigenetic, Differentiating, and Chemotherapeutic Agents Cooperatively Targets Tumor-Initiating Cells in Triple-Negative Breast Cancer.

Efforts to induce the differentiation of cancer stem cells through treatment with all-trans retinoic acid (ATRA) have yielded limited success, partially due to the epigenetic silencing of the retinoic acid receptor (RAR)-ß The histone deacetylase inhibitor entinostat is emerging as a promising antitumor agent when added to the standard-of-care treatment for breast cancer. However, the combination of epigenetic, cellular differentiation, and chemotherapeutic approaches against triple-negative breast cancer (TNBC) has not been investigated. In this study, we found that combined treatment of TNBC xenografts with entinostat, ATRA, and doxorubicin (EAD) resulted in significant tumor regression and restoration of epigenetically silenced RAR-ß expression. Entinostat and doxorubicin treatment inhibited topoisomerase II-ß (TopoII-ß) and relieved TopoII-ß-mediated transcriptional silencing of RAR-ß Notably, EAD was the most effective combination in inducing differentiation of breast tumor-initiating cells in vivo Furthermore, gene expression analysis revealed that the epithelium-specific ETS transcription factor-1 (ESE-1 or ELF3), known to regulate proliferation and differentiation, enhanced cell differentiation in response to EAD triple therapy. Finally, we demonstrate that patient-derived metastatic cells also responded to treatment with EAD. Collectively, our findings strongly suggest that entinostat potentiates doxorubicin-mediated cytotoxicity and retinoid-driven differentiation to achieve significant tumor regression in TNBC. Cancer Res; 76(7); 2013-24. ©2016 AACR.

Cytotechnologist Performance for Screening Hürthle Cell Atypia in Indeterminate Thyroid Fine-Needle Aspirates.

OBJECTIVES: We have previously shown that specimens diagnosed as containing Hürthle cells have a 12% chance of being malignant if they are classified as atypia of undetermined significance (AUS-HC). The identification of Hürthle cells by cytotechnologists (CTs) during screening can improve cytopathologist efficiency and may prevent diagnostic errors due to the oversights of focal findings. Here, we examine the performance of our institutional CTs when screening for Hürthle cell atypia in thyroid fine-needle aspiration (FNA) specimens. STUDY DESIGN: Information on 8,814 thyroid cytopathology specimens was retrieved for a 10-year period. Specimens were screened by 1 of 11 CTs. A subsample of cases was categorized either as AUS-HC or suspicious for Hürthle cell neoplasm. RESULTS: AUS-HC screening diagnoses were more likely to be downgraded to benign but less likely to be upgraded compared to AUS diagnoses with nuclear or microfollicular atypia. AUS-HC represents almost all papillary thyroid carcinoma (PTC) screening diagnoses downgraded to the AUS category, which suggests that even low levels of Hürthle cell atypia can result in PTC being included in the differential diagnosis. CONCLUSION: Overall, there are few major discrepancies between CT and pathologist diagnoses for specimens containing Hürthle cell atypia.

Zinc absorption from a low-phytic acid maize.

BACKGROUND: Phytic acid reduction in cereal grains has been accomplished with plant genetic techniques. These low-phytic acid grains provide a strategy for improving the mineral (eg, zinc) status in populations that are dependent on grains, including maize (Zea mays L.), as major dietary staples. OBJECTIVE: The objective was to compare the fractional absorption of zinc from polenta prepared from maize low in phytic acid with that prepared from a wild-type isohybrid maize (control) after short-term consumption by adults whose habitual diet is low in phytic acid. DESIGN: Healthy adults served as their own control subjects in a crossover design. All meals on 1 d consisted of polenta prepared from a low-phytic acid maize homozygous for the recessive low phytic acid 1-1 (lpa1-1). On the preceding or following day, all meals consisted of polenta prepared from a sibling isohybrid homozygous wild-type maize with a "normal" phytic acid content. The low-phytic acid maize contained approximately 60% less phytic acid than did the wild-type maize. All test meals were extrinsically labeled with zinc stable-isotope tracers. The fractional absorption of zinc was determined on the basis of fecal enrichment. RESULTS: The molar ratios of phytic acid to zinc in the polenta prepared from lpa1-1 maize and the wild-type maize were 17:1 and 36:1, respectively. The corresponding fractional absorptions of zinc were 0.30 +/- 0.13 and 0.17 +/- 0.11, respectively (P < 0.005). CONCLUSION: Substitution of a low-phytic acid grain in a maize-based diet is associated with a substantial increase in zinc absorption.

Percutaneous intraspinal navigation: feasibility study of a new and minimally invasive approach to the spinal cord and brain in cadavers.

We describe a percutaneous approach for cerebral surgical access. After lumbar puncture, the spinal subarachnoid space was traversed by using standard angiographic guidewire techniques until the introducer catheters were in the intracranial space. Under fluoroscopic guidance, the intracranial subarachnoid space was navigated, and the ventricular system entered. Subarachnoid placement was confirmed with contrast-enhanced digital angiography. Placement anterior to the brain stem was confirmed in both cadavers during dissection, and spinal navigation without cord damage from the anterior or posterior approach was confirmed in one. Percutaneous intraspinal navigation is a new route of access for cerebrospinal surgery that has many potential applications.

Percutaneous translumbar spinal cord compression injury in a dog model that uses angioplasty balloons: MR imaging and histopathologic findings.

BACKGROUND AND PURPOSE: Previous animal models for spinal cord injury required laminectomy and exposure of the spinal cord to create direct trauma, compromising imaging by both surgical artifact and the nature of the production of the injury. Our purpose was to study a model that uses percutaneous intraspinal navigation with an angioplasty balloon, providing a controlled degree of spinal cord compression and allowing improved MR imaging of spinal cord injury. METHODS: Nine mongrel dogs were studied. MR images were obtained of six dogs after technique development in three dogs. Angioplasty balloons measuring 7 or 4 mm in diameter and 2 cm in length were placed in the midthoracic subarachnoid space. Imaging was performed by using a 1.5-T MR imaging unit before and after balloon inflation. The balloon was inflated within 5 seconds and deflated after 30 minutes. T1- and T2-weighted and contrast-enhanced images were acquired. Spinal cords were submitted for pathologic examination. RESULTS: All four animals with 7-mm balloons experienced hemorrhage, and three had axonal injury revealed by histopathologic examination. One of two animals with 4-mm balloons experienced no injury, and one had axonal injury without hemorrhage. Regional parenchymal enhancement was seen in two of the animals with 7-mm balloons. CONCLUSION: This percutaneous spinal cord injury model results in a graduating degree of injury. It differs from previous techniques by avoiding surgical exposure and the associated artifacts, yet it offers histopathologic findings similar to those of human spinal cord injury. The canine spinal cord is amenable to MR imaging with clinical imaging units. Further evaluations with various durations of compression and various balloon sizes are warranted.

Percutaneous translumbar spinal cord compression injury in dogs from an angioplasty balloon: MR and histopathologic changes with balloon sizes and compression times.

BACKGROUND AND PURPOSE: Our previous model of spinal cord injury (SCI) included six dogs undergoing 30-minute compression with a balloon in the subarachnoid space. We determined whether various balloon sizes and compression times creates a gradation of injuries. METHODS: In 17 dogs (including our original six), angioplasty balloons 2, 4, or 7 mm in diameter (2 cm long) were inflated at T6 for 30, 120, or 240 minutes. T1- and T2-weighted, gadolinium-enhanced, and short-tau inversion recovery (STIR) MR images were obtained at 1.5 T. Spinal canal occlusion (SCO) was measured as balloon area-spinal cord area. Hematoxylin-eosin and beta amyloid precursor protein staining were performed to demonstrate hemorrhage and axonal injury, respectively. Injuries were scored as mild, moderate, or severe. Trends were assessed with one-way analysis of variance. RESULTS: SCO was 12.5-20% for 2-mm balloons, 28-56% for 4 mm, and 62-82% for 7 mm. No abnormalities were seen with SCO <30%. T1- and T2-weighted images had the poorest diagnostic performance; STIR images were best for predicting hemorrhage and axonal injury. Hemorrhage was demonstrated more frequently than was axonal injury. SCO (P < .0001) and hemorrhage (P = .002) significantly increased with balloon size. Longer inflation times tended to increase injuries for a given size, but differences were not significant. CONCLUSION: Compression injuries depended on the level of SCO. The compression times tested had less effect than the degree of compression. The value of 1.5-T MR imaging varied with the sequence and improved with contrast enhancement. STIR images showed SCIs not otherwise detected.

MR-guided catheter navigation of the intracranial subarachnoid space.

Percutaneous intraspinal navigation (PIN) is a new minimally invasive approach to the CNS. The authors studied the utility of MR-guided intracranial navigation following access to the subarachnoid compartment via PIN. The passive tracking technique was employed to visualize devices during intracranial navigation. Under steady-state free precession (SSFP) MR-guidance a microcatheter-microguidewire was successfully navigated to multiple brain foci in two cadavers. SSFP MR fluoroscopy possesses adequate contrast and temporal resolution to allow MR-guided intracranial navigation.