Quantifying Tumor and Vasculature Deformations during Laryngoscopy.

Retractors and scopes used in head and neck surgery to provide adequate surgical exposure also deform critical structures in the region. Surgeons typically use preoperative imaging to plan and guide their tumor resections, however the large tissue deformation resulting from placement of retractors and scopes reduces the utility of preoperative imaging as a reliable roadmap. We quantify the extent of tumor and vasculature deformation in patients with tumors of the larynx and pharynx undergoing diagnostic laryngoscopy. A mean tumor displacement of 1.02 cm was observed between the patients' pre- and intra-operative states. Mean vasculature displacement at key bifurcation points was 0.99 cm. Registration to the hyoid bone can reduce tumor displacement to 0.67 cm and improve carotid stem angle deviations but increase overall vasculature displacement. The large deformation results suggest limitations in reliance on preoperative imaging and that using specific landmarks intraoperatively or having more intraoperative information could help to compensate for these deviations and ultimately improve surgical success.

CT for estimating adequacy of lymph node dissection in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Indices obtained from lymph node dissection specimens, specifically lymph node yield (LNY) and lymph node ratio (LNR), have prognostic significance in the setting of head and neck squamous cell carcinoma (HNSCCa). However, there are currently no validated tools to estimate adequacy of planned lymph node dissection using preoperative data. The present study sought to evaluate CT-derived estimates of lymphatic tissue volumes as a preoperative tool to guide cervical node dissection. METHODS: Fifteen cervical lymph node dissections were performed in 14 subjects with HNSCCa. Preoperative CT-derived estimates of lymphatic tissue volumes were compared with gross pathology tissue volume estimates and pathologically-determined LNY. RESULTS: Resected tissue volume (calculated using the triaxial ellipsoid method) correlates with CT-derived preoperative lymphatic volume estimates (r = 0.74, p = 0.003) while LNY does not(r = - 0.12, p = 0.67). When excluding pathologically enlarged lymph nodes ("refined" data), a negative correlation was observed between refined CT-derived volume estimates and refined LNY (r = - 0.65, p = 0.009). CONCLUSION: In the setting of cervical lymph node dissection, CT-derived lymphatic volume estimates correlate with resected tissue volume, but refined CT-derived volume estimates correlate negatively with refined LNY. TRIAL REGISTRATION: Retrospectively registered. LEVEL OF EVIDENCE: 4.

First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip.

OBJECTIVE: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the 'OxyChip', as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing. METHODS: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry. RESULTS: Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4-128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6-73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5-144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation. CONCLUSIONS: Measurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.

Diagnosis and management of oral cavity lipoblastoma and lipoblastomatosis in an 8-month-old boy.

Lipoblastoma/lipoblastomatosis presents some unique diagnostic and therapeutic challenges when encountered in the oral cavity. In these rare cases, diagnostic confirmation with molecular testing and a conservative surgical resection can contribute to successful management.

Clinicopathologic and Genomic Characterization of Inflammatory Myofibroblastic Tumors of the Head and Neck: Highlighting a Novel Fusion and Potential Diagnostic Pitfall.

Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is available about its clinicopathologic and molecular characteristics in these subsites. Therefore, we analyzed a cohort of head and neck IMTs through a multi-institutional approach. Fourteen cases were included in the provisional cohort, but 1 was excluded after molecular analysis prompted reclassification. Patients in the final cohort included 7 males and 6 females, with a mean age of 26.5 years. Tumors were located in the larynx (n=7), oral cavity (n=3), pharynx (n=2), and mastoid (n=1). Histologically, all tumors showed neoplastic spindle cells in storiform to fascicular patterns with associated chronic inflammation, but the morphologic spectrum was wide, as is characteristic of IMT in other sites. An underlying fusion gene event was identified in 92% (n=11/12) of cases and an additional case was ALK-positive by IHC but could not be evaluated molecularly. ALK represented the driver in all but 1 case. Rearrangement of ALK, fused with the TIMP3 gene (n=6) was most commonly detected, followed by 1 case each of the following fusion gene partnerships: TPM3-ALK, KIF5B-ALK, CARS-ALK, THBS1-ALK, and a novel alteration, SLC12A2-ROS1. The excluded case was reclassified as spindle cell rhabdomyosarcoma after detection of a FUS-TFCP2 rearrangement and retrospective immunohistochemical confirmation of rhabdomyoblastic differentiation, illustrating an important diagnostic pitfall. Two IMT patients received targeted therapy with crizotinib, with a demonstrated radiographic response. One tumor recurred but none metastasized. These results add to the growing body of evidence that kinase fusions can be identified in the majority of IMTs and that molecular analysis can lead to increased diagnostic accuracy and broadened therapeutic options for patients.

Tensor Veli Palatinopexy as a Novel Treatment for Eustachian Tube Dysfunction: A Cadaveric Feasibility Study.

OBJECTIVE: To demonstrate the feasibility of a novel procedure whereby a suture is placed transorally in the tensor veli palatini muscle to tighten it, thereby dilating the cartilaginous portion of the eustachian tube (ET). STUDY DESIGN: The study design was a prospective cadaveric experiment to examine the feasibility of a novel treatment for ET dysfunction. SETTING: Academic medical center in a research-oriented operating room with intraoperative computed tomography (CT) capabilities. METHODS: Seven fresh-frozen cadaver heads were obtained, each of which was thawed for 36 hours prior to use. The preprocedural volumes of the cartilaginous ET were measured by filling the ET with an iodine-containing radiocontrast agent via the nasopharynx and then obtaining CT images. Submucosal flaps in the soft palate were raised, and sutures were placed in the tensor veli palatini bilaterally to increase tension. After completion of the procedure, contrast placement and CT imaging were repeated. Three-dimensional models of the ETs were created, and the volumes were measured and compared. RESULTS: Of the 14 ETs evaluated, 13 showed an increase in postprocedure volume. On average, postprocedure volumes showed a 57% increase from preprocedure volumes (mean relative change, 57.1%; P = .013). CONCLUSION: Placement of a tension-holding suture in the tensor veli palatini muscle can reliably dilate the cartilaginous portion of the ET. Such a procedure may be useful in the treatment of ET dysfunction.

OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in 24 Patients.

Introduction: Tumor hypoxia confers both a poor prognosis and increased resistance to oncologic therapies, and therefore, hypoxia modification with reliable oxygen profiling during anticancer treatment is desirable. The OxyChip is an implantable oxygen sensor that can detect tumor oxygen levels using electron paramagnetic resonance (EPR) oximetry. We report initial safety and feasibility outcomes after OxyChip implantation in a first-in-humans clinical trial (NCT02706197, www.clinicaltrials.gov). Materials and Methods: Twenty-four patients were enrolled. Eligible patients had a tumor ≤ 3 cm from the skin surface with planned surgical resection as part of standard-of-care therapy. Most patients had a squamous cell carcinoma of the skin (33%) or a breast malignancy (33%). After an initial cohort of six patients who received surgery alone, eligibility was expanded to patients receiving either chemotherapy or radiotherapy prior to surgical resection. The OxyChip was implanted into the tumor using an 18-G needle; a subset of patients had ultrasound-guided implantation. Electron paramagnetic resonance oximetry was carried out using a custom-built clinical EPR scanner. Patients were evaluated for associated toxicity using the Common Terminology Criteria for Adverse Events (CTCAE); evaluations started immediately after OxyChip placement, occurred during every EPR oximetry measurement, and continued periodically after removal. The OxyChip was removed during standard-of-care surgery, and pathologic analysis of the tissue surrounding the OxyChip was performed. Results: Eighteen patients received surgery alone, while five underwent chemotherapy and one underwent radiotherapy prior to surgery. No unanticipated serious adverse device events occurred. The maximum severity of any adverse event as graded by the CTCAE was 1 (least severe), and all were related to events typically associated with implantation. After surgical resection, 45% of the patients had no histopathologic findings specifically associated with the OxyChip. All tissue pathology was "anticipated" excepting a patient with greater than expected inflammatory findings, which was assessed to be related to the tumor as opposed to the OxyChip. Conclusion: This report of the first-in-humans trial of OxyChip implantation and EPR oximetry demonstrated no significant clinical pathology or unanticipated serious adverse device events. Use of the OxyChip in the clinic was thus safe and feasible.

Improving target localization during trans-oral surgery with use of intraoperative imaging.

PURPOSE: Trans-oral surgery provides a less invasive means for the surgical management of upper aerodigestive tract malignancies but is limited in its ability to readily assess submucosal tumor extent and location of critical structures intraoperatively. We sought to determine surgeons' baseline target localization accuracy during operative laryngoscopy with preoperative imaging alone and then assess for improvement in localization accuracy when presented with intraoperative CT imaging capturing soft tissue deformation. METHODS: Fiducial beads were placed submucosally in four cadaver heads. "Preoperative" (PO) and "intraoperative" (IO) neck CTs were acquired before and during suspension laryngoscopy using a CT-compatible laryngoscopy system. Surgeons attempted to localize submucosal fiducials beads using pins based on sequential review of PO and IO images. RESULTS: Mean total error (TE) decreased from 12.8 ± 9.9 to 10 ± 7.5 mm from PO to IO (P < 0.001), respectively. TE for base of tongue and vallecula decreased by 1.7 ± 6.7 mm (P = 0.015). Right-sided structures were most exposed by scope positioning and experienced a TE reduction of 4.8 ± 9.3 mm (P < 0.001). Task completion time decreased from PO to IO by 26% (P < 0.001). CONCLUSIONS: Intraoperative imaging significantly improves localization accuracy and task efficiency when targeting submucosal beads in cadaver heads during operative laryngoscopy.

Multi-modal Framework for Image-guided Trans-oral Surgery with Intraoperative Imaging and Deformation Modeling.

Treatment of throat cancers have improved due to minimally-invasive trans-oral approaches. Surgeons rely on preoperative imaging to guide their resection; however, large tissue deformations occur during trans-oral procedures due to placement of necessary retractors and laryngoscopes which hinders the surgeon's ability to accurately assess tumor extent and location of critical structures. We propose an image-guided framework utilizing intraoperative imaging and deformation modeling to improve surgeon accuracy and confidence. A CT-compatible laryngoscopy system previously developed was evaluated in this framework. Intraoperative images were acquired during laryngoscopy; force-sensing capabilities were enabled in the laryngoscope; and tracking of the scope and anatomic features was trialed. Tissue deformation and displacement were quantified and determined to be extensive, with values <; 4.6 cm in the tongue, <; 1.8 cm in bony structures, and <; 108.9 cm3 in airway volume change. Surgical navigation using intraoperative imaging and tracking was evaluated. Preliminary assessment of deformation modeling showed potential to supplement intraoperative imaging. Future work will involve streamlined integration of the components of this framework.

Radiation exposure alters airway deformability and bony structure displacement during laryngoscopy.

BACKGROUND: Prior therapeutic radiation exposure in the setting of head and neck malignancies is associated with difficult airway instrumentation. We sought to characterize the anatomic changes that produce this phenotype. STUDY DESIGN: Retrospective review. METHODS: Five individuals with prior radiation therapy to the upper aerodigestive tract (previously irradiated) and 10 with no prior history of therapeutic radiation exposure (nonirradiated) were enrolled. Computed tomography images obtained before and during laryngoscope insertion ("uninstrumented" and "instrumented", respectively) were used to reconstruct three-dimensional representations of the pharyngeal airway, hyoid, and mandible. RESULTS: In the instrumented state, pharyngeal airway volumes were significantly greater in nonirradiated subjects relative to previously irradiated subjects (P = .01), and overall translation of both the hyoid and mandible was also greater in nonirradiated subjects (P = .01 and .04, respectively). CONCLUSION: Individuals with prior therapeutic radiation exposure to the upper aerodigestive tract differ from nonirradiated subjects with respect to airway deformation and bony structure translation during laryngoscopy. LEVEL OF EVIDENCE: 4.

Changes in Primary Care Health Care Utilization after Inclusion of Epidemiologic Data in Lumbar Spine MR Imaging Reports for Uncomplicated Low Back Pain.

Purpose To determine whether inclusion of an epidemiologic statement in radiology reports of lumbar magnetic resonance (MR) imaging influences downstream health care utilization in the primary care population. Materials and Methods Beginning July 1, 2013, a validated epidemiologic statement regarding prevalence of common findings in asymptomatic patients was included in all lumbar MR imaging reports at a tertiary academic medical center. Data were collected from July 1, 2012, through June 30, 2014, and retrospective analysis was completed in September 2016. The electronic medical record was reviewed to capture health care utilization rates in patients for 1 year after index MR imaging. Of 4527 eligible adult patients with low back pain referred for lumbar spine MR imaging during the study period, 375 patients had their studies ordered by in-network primary care providers, did not have findings other than degenerative disease, and had at least one follow-up encounter within the system within 1 year of index MR imaging. In the before-and-after study design, a pre-statement-implementation cohort was compared with a post-statement-implementation cohort by using univariate and multivariate statistical models to evaluate treatment utilization rates in these groups. Results Patients in the statement group were 12% less likely to be referred to a spine specialist (137 of 187 [73%] vs 159 of 188 [85%]; P = .007) and were 7% less likely to undergo repeat imaging (seven of 187 [4%] vs 20 of 188 [11%]; P = .01) compared with patients in the nonstatement group. The intervention was not associated with any change in narcotic prescription (53 of 188 [28%] vs 54 of 187 [29%]; P = .88) or with the rate of low back surgery (24 of 188 [13%] vs 16 of 187 [9%]; P = .19). Conclusion In this study, inclusion of a simple epidemiologic statement in lumbar MR imaging reports was associated with decreased utilization in high-cost domains of low back pain management. © RSNA, 2018.

Methotrexate encephalopathy: Two cases in adult cancer patients, who recovered with pathophysiologically based therapy.

BACKGROUND/OBJECTIVES: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. RESULTS: Case 1: A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2: A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high-dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. CONCLUSIONS: These two cases suggest that N-methyl d-aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity.

Symptomatic Lumbar Facet Synovial Cysts: Clinical Outcomes Following Percutaneous CT-Guided Cyst Rupture with Intra-articular Steroid Injection.

PURPOSE: To evaluate clinical outcomes following percutaneous rupture of symptomatic lumbar facet synovial cysts (LFSCs) with intra-articular steroid injection. MATERIALS AND METHODS: In this retrospective review, 44 consecutive patients with symptomatic LFSCs received primary treatment with CT-guided synovial cyst rupture with intra-articular steroid injection. Outcomes questionnaires were obtained before and 1, 4, 26, and 52 weeks after LFSC rupture. Assessment included pain medication use and numeric rating scale (NRS), Oswestry Disability Index (ODI), and 12-item short form health survey (SF-12) physical and mental composite scores (PCS and MCS). Clinical endpoint was 52-week survey response or surgery. RESULTS: LFSC rupture was technically successful in 84% (37/44) of cases. Clinical endpoint was reached in 68% (30/44) of patients with 82% overall 1-year follow-up. Lumbar spine surgery was performed in 25% (11/44) of patients within 1 year after procedure. Mean NRS, ODI, and SF-12 PCS demonstrated significant improvement at all follow-up time points (P < .001). At 52-week follow-up, NRS decreased from 8.1 to 3.7 (P < .001), ODI improved from 35 to 24 (P = .006), and SF-12 PCS improved from 31 to 42 (P < .001). Daily pain medication decreased from 71% (31/44) of patients before procedure to 29% (9/26) at 52-week follow-up (P = .012). History of prior lumbar intervention was associated with poorer LFSC rupture success (P = .025) and ODI (P = .047). CONCLUSIONS: NRS, ODI, and SF-12 PCS indices improved and pain medication use decreased significantly at all time points over 1-year follow-up after percutaneous rupture of symptomatic LFSCs with intra-articular steroid injection.

Value of Imaging Part I: Perspectives for the Academic Radiologist.

With payers and policymakers increasingly scrutinizing the value of medical imaging, opportunities abound for radiologists and radiology health services researchers to meaningfully and rigorously demonstrate value. Part one of this two-part series on the value of imaging explores the concept of value in health care from the perspective of multiple stakeholders and discusses the opportunities and challenges for radiologists and health service researchers to demonstrate value. The current absence of meaningful national value metrics also presents an opportunity for radiologists to take the lead on the discussions of these metrics that may serve as the basis for future value-based payments. As both practitioners and investigators, radiologists should consider the perspectives of multiple stakeholders in all they do-interdisciplinary support and cooperation are essential to the success of value-focused imaging research and initiatives that improve patient outcomes. Radiology departments that align their cultures, infrastructures, and incentives to support these initiatives will greatly increase their chances of being successful in these endeavors.

The Value of Imaging Part II: Value beyond Image Interpretation.

Although image interpretation is an essential part of radiologists' value, there are other ways in which we contribute to patient care. Part II of the value of imaging series reviews current initiatives that demonstrate value beyond the image interpretation. Standardizing processes, reducing the radiation dose of our examinations, clarifying written reports, improving communications with patients and providers, and promoting appropriate imaging through decision support are all ways we can provide safer, more consistent, and higher quality care. As payers and policy makers push to drive value, research that demonstrates the value of these endeavors, or lack thereof, will become increasingly sought after and supported.

Genetics of glioblastoma: a window into its imaging and histopathologic variability.

Glioblastoma is a highly malignant brain tumor that relentlessly defies therapy. Efforts over the past decade have begun to tease out the biochemical details that lead to its aggressive behavior and poor prognosis. There is hope that this new understanding will lead to improved treatment strategies for patients with glioblastoma, in the form of targeted, molecularly based therapies that are individualized to specific changes in individual tumors. However, these new therapies have the potential to fundamentally alter the biologic behavior of glioblastoma and, as a result, its imaging appearance. Knowledge about common genetic alterations and the resultant cellular and tissue changes (ie, induced angiogenesis and abnormal cell survival, proliferation, and invasion) in glioblastomas is important as a basis for understanding imaging findings before treatment. It is equally critical that radiologists understand which genetic pathway is targeted by each specific therapeutic agent or class of agents in order to accurately interpret changes in the imaging appearances of treated tumors.

Internal structure in pineal cysts on high-resolution magnetic resonance imaging: not a sign of malignancy.

OBJECT: In this paper, the authors' goal was to determine whether benign pineal cysts have smooth walls or internal structure on high-resolution MR imaging and to evaluate their imaging characteristics on FLAIR images. METHODS: The authors retrospectively reviewed the MR imaging findings in 60 consecutive patients who were reported to have pineal cysts over a 19-month period. Patients were identified retrospectively using a word search of radiology reports. Of these 60 patients, 24 with stable follow-up imaging or pathological proof of a pineal cyst were included in this study. In all cases, axial or sagittal FLAIR images were available, and in 10 of 24 patients the authors obtained sagittal images using fast imaging employing steady-state acquisition (FIESTA). For those cases in which FIESTA studies were obtained, the authors classified the cysts into 1 of 4 categories based on their appearance. Eighteen of 24 cases were performed with intravenous contrast. RESULTS: Of the 24 cases, 21 had signal intensity on FLAIR images that differed from that of CSF. Of the 10 cases with FIESTA, 6 had evidence of internal structure within the pineal cyst. The authors found it of interest that 20 of the 24 patients were female. CONCLUSIONS: Although the presence of a thin wall supports the diagnosis of a benign pineal cyst, fine internal septations or small internal cysts are common on high-resolution MR imaging and this finding should not be considered evidence of an underlying tumor. It is typical for pineal cysts to have relaxation times that differ from CSF as determined by FLAIR imaging.