Fusion of Computed Tomography and PROPELLER Diffusion-Weighted Magnetic Resonance Imaging for the Detection and Localization of Middle Ear Cholesteatoma.

Importance: A method to optimize imaging of cholesteatoma by combining the strengths of available modalities will improve diagnostic accuracy and help to target treatment. Objective: To assess whether fusing Periodically Rotated Overlapping Parallel Lines With Enhanced Reconstruction (PROPELLER) diffusion-weighted magnetic resonance imaging (DW-MRI) with corresponding temporal bone computed tomography (CT) images could increase cholesteatoma diagnostic and localization accuracy across 6 distinct anatomical regions of the temporal bone. Design, Setting, and Participants: Case series and preliminary technology evaluation of adults with preoperative temporal bone CT and PROPELLER DW-MRI scans who underwent surgery for clinically suggested cholesteatoma at a tertiary academic hospital. When cholesteatoma was encountered surgically, the precise location was recorded in a diagram of the middle ear and mastoid. For each patient, the 3 image data sets (CT, PROPELLER DW-MRI, and CT-MRI fusion) were reviewed in random order for the presence or absence of cholesteatoma by an investigator blinded to operative findings. Main Outcomes and Measures: If cholesteatoma was deemed present on review of each imaging modality, the location of the lesion was mapped presumptively. Image analysis was then compared with surgical findings. Results: Twelve adults (5 women and 7 men; median [range] age, 45.5 [19-77] years) were included. The use of CT-MRI fusion had greater diagnostic sensitivity (0.88 vs 0.75), positive predictive value (0.88 vs 0.86), and negative predictive value (0.75 vs 0.60) than PROPELLER DW-MRI alone. Image fusion also showed increased overall localization accuracy when stratified across 6 distinct anatomical regions of the temporal bone (localization sensitivity and specificity, 0.76 and 0.98 for CT-MRI fusion vs 0.58 and 0.98 for PROPELLER DW-MRI). For PROPELLER DW-MRI, there were 15 true-positive, 45 true-negative, 1 false-positive, and 11 false-negative results; overall accuracy was 0.83. For CT-MRI fusion, there were 20 true-positive, 45 true-negative, 1 false-positive, and 6 false-negative results; overall accuracy was 0.90. Conclusions and Relevance: The poor anatomical spatial resolution of DW-MRI makes precise localization of cholesteatoma within the middle ear and mastoid a diagnostic challenge. This study suggests that the bony anatomic detail obtained via CT coupled with the excellent sensitivity and specificity of PROPELLER DW-MRI for cholesteatoma can improve both preoperative identification and localization of disease over DW-MRI alone.

Evaluating the utility of non-echo-planar diffusion-weighted imaging in the preoperative evaluation of cholesteatoma: a meta-analysis.

OBJECTIVES/HYPOTHESIS: To describe the accuracy of non-echo-planar diffusion-weighted magnetic resonance imaging (DW MRI) in identifying middle ear cholesteatoma. STUDY DESIGN: A meta-analysis of the published literature. METHODS: A systematic review of the literature was performed to identify studies in which patients suspected of having middle ear cholesteatoma underwent DW MRI scans prior to surgery. A meta-analysis of the included studies was performed. RESULTS: Ten published articles (342 patients) met inclusion criteria. Cholesteatoma was confirmed in 234 patients, of which 204 were detected by DW MRI (true positives) and 30 were not (false negatives). One hundred eight patients did not have cholesteatoma on surgical examination, and of these 100 were correctly identified by MRI (true negatives) whereas eight were not (false positives). The overall sensitivity of DW MRI in detecting cholesteatoma was 0.94 (confidence interval, 0.80-0.98) and specificity 0.94 (confidence interval, 0.85-0.98). DW MRI sequences could not reliably detect cholesteatomas under 3 mm in size. CONCLUSIONS: Non-echo-planar DW MRI is highly sensitive and specific in identifying middle ear cholesteatoma. DW MRI may help to stratify patients into groups of who would benefit from early second-look surgery and those who could be closely observed. LEVEL OF EVIDENCE: 2a.

Dural arteriovenous fistula following translabyrinthine resection of cerebellopontine angle tumors: report of two cases.

We describe two cases of dural arteriovenous fistula (DAVF) developing in a delayed fashion after translabyrinthine resection of cerebellopontine angle tumors. Two patients in an academic tertiary referral center, a 46-year-old woman and a 67-year-old man, underwent translabyrinthine resection of a 2-cm left vestibular schwannoma and a 4-cm left petrous meningioma, respectively. Both patients subsequently developed DAVF, and in each case the diagnosis was delayed despite serial imaging follow-up. In one patient, cerebrospinal fluid diversion before DAVF was identified as the cause of her intracranial hypertension; the other patient was essentially asymptomatic but with a high risk of hemorrhage due to progression of cortical venous drainage. Endovascular treatment was effective but required multiple sessions due to residual or recurrent fistulas. Dural arteriovenous fistula is a rare complication of translabyrinthine skull base surgery. Diagnosis requires a high index of clinical suspicion and an understanding of subtle imaging findings that may be present on follow-up studies performed for tumor surveillance. Failure to recognize this complication may lead to misguided interventions for treatment of hydrocephalus and other complications, as well as ongoing risks related to venous hypertension and intracranial hemorrhage. As this condition is generally curable with neurointerventional and/or surgical methods, timely diagnosis and treatment are essential.

Controlled steroid delivery via bioabsorbable stent: safety and performance in a rabbit model.

BACKGROUND: Middle turbinate lateralization, adhesions, and inflammation are causes of suboptimal sinus patency following surgery. A bioabsorbable drug-eluting stent has been developed to maintain sinus patency while providing controlled steroid delivery to the sinus mucosa. The aim of this study was to characterize the in vivo drug delivery efficacy and tolerance of this stent in a rabbit model. METHODS: Bioabsorbable stents coated with mometasone furoate were placed bilaterally in the maxillary sinuses of 31 rabbits via dorsal maxillary sinusotomy. Animals were sacrificed between 5 days and 18 weeks postoperatively. Efficacy was assessed by measuring tissue concentrations of steroid in maxillary sinus and nasal mucosa and by measurement of plasma steroid concentrations. Tolerance was assessed by histological evaluation of the sinus mucosa at different time points. RESULTS: Therapeutic mucosal drug concentrations were attained in a time-dependent fashion (range 175-28,189 ng/g). Plasma drug concentrations were generally near or below the lower limit of quantification (15 pg/mL). Histopathological examination of the mucosa showed no differences in the reaction to steroid-coated stents versus nondrug-coated control stents, with inflammation, epithelial ulceration, and bony reaction ranging from none to mild at all time points. Microscopic fungal hyphae were noted in a small proportion of both treatment and control sinuses, without evidence of associated adverse tissue reaction. CONCLUSIONS: In a rabbit model, mometasone-coated bioabsorbable stents are able to provide local steroid delivery with negligible systemic absorption. Corticosteroid-eluting stents may prove useful following endoscopic sinus surgery in maintaining sinus patency and reducing inflammation.

HPD: an online integrated human pathway database enabling systems biology studies.

BACKGROUND: Pathway-oriented experimental and computational studies have led to a significant accumulation of biological knowledge concerning three major types of biological pathway events: molecular signaling events, gene regulation events, and metabolic reaction events. A pathway consists of a series of molecular pathway events that link molecular entities such as proteins, genes, and metabolites. There are approximately 300 biological pathway resources as of April 2009 according to the Pathguide database; however, these pathway databases generally have poor coverage or poor quality, and are difficult to integrate, due to syntactic-level and semantic-level data incompatibilities. RESULTS: We developed the Human Pathway Database (HPD) by integrating heterogeneous human pathway data that are either curated at the NCI Pathway Interaction Database (PID), Reactome, BioCarta, KEGG or indexed from the Protein Lounge Web sites. Integration of pathway data at syntactic, semantic, and schematic levels was based on a unified pathway data model and data warehousing-based integration techniques. HPD provides a comprehensive online view that connects human proteins, genes, RNA transcripts, enzymes, signaling events, metabolic reaction events, and gene regulatory events. At the time of this writing HPD includes 999 human pathways and more than 59,341 human molecular entities. The HPD software provides both a user-friendly Web interface for online use and a robust relational database backend for advanced pathway querying. This pathway tool enables users to 1) search for human pathways from different resources by simply entering genes/proteins involved in pathways or words appearing in pathway names, 2) analyze pathway-protein association, 3) study pathway-pathway similarity, and 4) build integrated pathway networks. We demonstrated the usage and characteristics of the new HPD through three breast cancer case studies. CONCLUSION: HPD http://bio.informatics.iupui.edu/HPD is a new resource for searching, managing, and studying human biological pathways. Users of HPD can search against large collections of human biological pathways, compare related pathways and their molecular entity compositions, and build high-quality, expanded-scope disease pathway models. The current HPD software can help users address a wide range of pathway-related questions in human disease biology studies.

Analysis of intracochlear new bone and fibrous tissue formation in human subjects with cochlear implants.

OBJECTIVES: In this study we aimed to evaluate new bone and new fibrous tissue formation in the inner ear following cochlear implantation. METHODS: Twelve temporal bones from patients who underwent cochlear implantation during life were prepared for histologic study. The specimens were reconstructed by both 2-dimensional and 3-dimensional methods. These reconstructions were used to calculate the total volume and distribution of new bone and new fibrous tissue in the cochlea, the number of spiral ganglion cells, and other histopathologic parameters. Clinical data, including the last-recorded word recognition scores, were obtained from the patients' medical records. RESULTS: New bone and new fibrous tissue were found in all 12 specimens, particularly at the site of cochleostomy. There was a significant correlation between overall damage to the lateral cochlear wall and the total volume of intracochlear new tissue (Spearman rho = .853; p = .0004). The total volume of new tissue did not correlate with word recognition scores or spiral ganglion cell counts. CONCLUSIONS: These preliminary results suggest that the degree of damage to the lateral cochlear wall may play an important role in influencing the amount of new tissue formation following cochlear implantation. Intracochlear new tissue does not appear to be an important determinant of performance as measured by word recognition scores or the total number of remaining spiral ganglion cells.

Anatomy of the round window and hook region of the cochlea with implications for cochlear implantation and other endocochlear surgical procedures.

HYPOTHESIS: The goal of this study was to create a three-dimensional model of the anatomy of the hook region to identify the optimal site for cochleostomy in cochlear implant surgery. BACKGROUND: The anatomy of the hook region is complex, and spatial relationships can be difficult to evaluate using two-dimensional histological slides or cadaveric temporal bones. METHODS: The right temporal bone of a 14-year-old adolescent boy was used to create a three-dimensional model. Sections containing the round window membrane (RWM) and surrounding cochlear structures were stained, digitized, and imported into a general purpose three-dimensional rendering and analysis software program (Amira, version 4.1). Three-dimensional models of the RWM, basilar membrane, osseous spiral lamina, spiral ligament, cochlear aqueduct, inferior cochlea vein, scala media, ductus reuniens, scala vestibuli, scala tympani, and surrounding bone were generated. The relationship between these structures and the RWM and adjacent otic capsule was evaluated. Histological sections from a different temporal bone were also analyzed. This temporal bone was sectioned in a plane perpendicular to the axis corresponding to the surgical view of the RWM, seen through the facial recess. RESULTS: The anteroinferior margin of the RWM or adjacent otic capsule was identified as the site for a cochleostomy that will avoid damage to critical cochlear structures and allow implantation directly into the scala tympani. The model can be downloaded from: https://research.meei.harvard.edu/otopathology/3dmodels. CONCLUSION: This three-dimensional model has implications for surgical procedures to the inner ear that aim to minimize insertional trauma.

Quantitative evaluation of new bone and fibrous tissue in the cochlea following cochlear implantation in the human.

The formation of new bone and fibrous tissue in the human inner ear following cochlear implantation was evaluated by computer-assisted 3-D reconstruction. Seven temporal bones from patients who in life had undergone cochlear implantation were prepared for histological study with the implant in situ. The specimens were sectioned in the axial plane at a thickness of 20 microm. At least every tenth section was digitally reconstructed in three dimensions and volumes of new bone and fibrous tissue were calculated per millimeter length of the cochlea. New bone and fibrous tissue were found in all seven specimens, particularly at the cochleostomy site. In addition, new bone and fibrous tissue had extended to variable lengths along the track of the cochlear implant and in some cases extended beyond the distal end of the implanted electrode. This methodology provides a quantitative tool for evaluation of new bone and fibrous tissue in the inner ear following implantation. This should assist in correlating psychophysical and speech perception tests with intracochlear pathology, evaluating both electrode design and the techniques of preserving residual auditory function.