Clinical Arterial Spin-Labeling MR Imaging to Screen for Typical and Atypical Neurodegenerative Disease in the New Era of Alzheimer Treatment.

The clinical standard of care in the diagnosis of neurodegenerative diseases relies on [18F] FDG-PET/CT or PET MR imaging. Limitations of FDG-PET include cost, the need for IV access, radiation exposure, and availability. Arterial spin-labeling MR imaging has been shown in research settings to be useful as a proxy for FDG-PET in differentiating Alzheimer disease from frontotemporal dementia. However, it is not yet widely used in clinical practice, except in cerebrovascular disease. Here, we present 7 patients, imaged with our routine clinical protocol with diverse presentations of Alzheimer disease and other neurodegenerative diseases, in whom arterial spin-labeling-derived reduced CBF correlated with hypometabolism or amyloid/tau deposition on PET. Our case series illustrates the clinical diagnostic utility of arterial spin-labeling MR imaging as a fast, accessible, and noncontrast screening tool for neurodegenerative disease. Arterial spin-labeling MR imaging can guide patient selection for subsequent PET or fluid biomarker work-up, as well as for possible therapy with antiamyloid monoclonal antibodies.

Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma.

PURPOSE: There are no effective medical therapies for patients with meningioma who progress beyond surgical and radiotherapeutic interventions. Somatostatin receptor type 2 (SSTR2) represents a promising treatment target in meningiomas. In this multicenter, single-arm phase II clinical study (NCT03971461), the SSTR2-targeting radiopharmaceutical 177Lu-DOTATATE is evaluated for its feasibility, safety, and therapeutic efficacy in these patients. PATIENTS AND METHODS: Adult patients with progressive intracranial meningiomas received 177Lu-DOTATATE at a dose of 7.4 GBq (200 mCi) every eight weeks for four cycles. 68Ga-DOTATATE PET-MRI was performed before and six months after the start of the treatment. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Secondary endpoints were safety and tolerability, overall survival (OS) at 12 months (OS-12), median PFS, and median OS. RESULTS: Fourteen patients (female = 11, male = 3) with progressive meningiomas (WHO 1 = 3, 2 = 10, 3 = 1) were enrolled. Median age was 63.1 (range 49.7-78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Seven patients (50%) achieved PFS-6. Best radiographic response by modified Macdonald criteria was stable disease (SD) in all seven patients. A >25% reduction in 68Ga-DOTATATE uptake (PET) was observed in five meningiomas and two patients. In one lesion, this corresponded to >50% reduction in bidirectional tumor measurements (MRI). CONCLUSIONS: Treatment with 177Lu-DOTATATE was well tolerated. The predefined PFS-6 threshold was met in this interim analysis, thereby allowing this multicenter clinical trial to continue enrollment. 68Ga-DOTATATE PET may be a useful imaging biomarker to assess therapeutic outcome in patients with meningioma.

Gallium-68-labeled fibroblast activation protein inhibitor-46 PET in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma: A phase 2, multicenter, single arm, open label non-randomized study protocol.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease prone to widespread metastatic dissemination and characterized by a desmoplastic stroma that contributes to poor outcomes. Fibroblast activation protein (FAP)-expressing Cancer-Associated Fibroblasts (CAFs) are crucial components of the tumor stroma, influencing carcinogenesis, fibrosis, tumor growth, metastases, and treatment resistance. Non-invasive tools to profile CAF identity and function are essential for overcoming CAF-mediated therapy resistance, developing innovative targeted therapies, and improved patient outcomes. We present the design of a multicenter phase 2 study (clinicaltrials.gov identifier NCT05262855) of [68Ga]FAPI-46 PET to image FAP-expressing CAFs in resectable or borderline resectable PDAC. METHODS: We will enroll up to 60 adult treatment-naïve patients with confirmed PDAC. These patients will be eligible for curative surgical resection, either without prior treatment (Cohort 1) or after neoadjuvant therapy (NAT) (Cohort 2). A baseline PET scan will be conducted from the vertex to mid-thighs approximately 15 minutes after administering 5 mCi (±2) of [68Ga]FAPI-46 intravenously. Cohort 2 patients will undergo an additional PET after completing NAT but before surgery. Histopathology and FAP immunohistochemistry (IHC) of initial diagnostic biopsy and resected tumor samples will serve as the truth standards. Primary objective is to assess the sensitivity, specificity, and accuracy of [68Ga]FAPI-46 PET for detecting FAP-expressing CAFs. Secondary objectives will assess predictive values and safety profile validation. Exploratory objectives are comparison of diagnostic performance of [68Ga]FAPI-46 PET to standard-of-care imaging, and comparison of pre- versus post-NAT [68Ga]FAPI-46 PET in Cohort 2. CONCLUSION: To facilitate the clinical translation of [68Ga]FAPI-46 in PDAC, the current study seeks to implement a coherent strategy to mitigate risks and increase the probability of meeting FDA requirements and stakeholder expectations. The findings from this study could potentially serve as a foundation for a New Drug Application to the FDA. TRIAL REGISTRATION: @ClinicalTrials.gov identifier NCT05262855.

Emerging diagnostic methods and imaging modalities in cushing's syndrome.

Endogenous Cushing's syndrome (CS) is a rare disease characterized by prolonged glucocorticoid excess. Timely diagnosis is critical to allow prompt treatment and limit long-term disease morbidity and risk for mortality. Traditional biochemical diagnostic modalities each have limitations and sensitivities and specificities that vary significantly with diagnostic cutoff values. Biochemical evaluation is particularly complex in patients whose hypercortisolemia fluctuates daily, often requiring repetition of tests to confirm or exclude disease, and when delineating CS from physiologic, nonneoplastic states of hypercortisolism. Lastly, traditional pituitary MRI may be negative in up to 60% of patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (termed "Cushing's disease" [CD]) whereas false positive pituitary MRI findings may exist in patients with ectopic ACTH secretion. Thus, differentiating CD from ectopic ACTH secretion may necessitate dynamic testing or even invasive procedures such as bilateral inferior petrosal sinus sampling. Newer methods may relieve some of the diagnostic uncertainty in CS, providing a more definitive diagnosis prior to subjecting patients to additional imaging or invasive procedures. For example, a novel method of cortisol measurement in patients with CS is scalp hair analysis, a non-invasive method yielding cortisol and cortisone values representing long-term glucocorticoid exposure of the past months. Hair cortisol and cortisone have both shown to differentiate between CS patients and controls with a high sensitivity and specificity. Moreover, advances in imaging techniques may enhance detection of ACTH-secreting pituitary adenomas. While conventional pituitary MRI may fail to identify microadenomas in patients with CD, high-resolution 3T-MRI with 3D-spoiled gradient-echo sequence has thinner sections and superior soft-tissue contrast that can detect adenomas as small as 2 mm. Similarly, functional imaging may improve the identification of ACTH-secreting adenomas noninvasively; Gallium-68-tagged corticotropin-releasing hormone (CRH) combined with PET-CT can be used to detect CRH receptors, which are upregulated on corticotroph adenomas. This technique can delineate functionality of adenomas in patients with CD from patients with ectopic ACTH secretion and false positive pituitary lesions on MRI. Here, we review emerging methods and imaging modalities for the diagnosis of CS, discussing their diagnostic accuracy, strengths and limitations, and applicability to clinical practice.

Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults.

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults < 50 years old. This trial was conducted in Equatorial Guinea and assessed the safety, tolerability, and immunogenicity of three direct venous inoculations of 1.8 × 106 or 2.7 × 106 PfSPZ, of PfSPZ Vaccine, or normal saline administered at 8-week intervals in a randomized, double-blind, placebo-controlled trial stratified by age (6-11 months and 1-5, 6-10, 11-17, 18-35, and 36-61 years). All doses were successfully administered. In all, 192/207 injections (93%) in those aged 6-61 years were rated as causing no or mild pain. There were no significant differences in solicited adverse events (AEs) between vaccinees and controls in any age group (P ≥ 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine.

MP-RAVE: IR-Prepared T1 -Weighted Radial Stack-of-Stars 3D GRE imaging with retrospective motion correction.

PURPOSE: To describe an inversion-recovery T1 -weighted radial stack-of-stars 3D gradient echo (GRE) sequence with comparable image quality to conventional MP-RAGE and to demonstrate how the radial acquisition scheme can be utilized for additional retrospective motion correction to improve robustness to head motion. METHODS: The proposed sequence, named MP-RAVE, has been derived from a previously described radial stack-of-stars 3D GRE sequence (RAVE) and includes a 180° inversion recovery pulse that is generated once for every stack of radial views. The sequence is combined with retrospective 3D motion correction to improve robustness. The effectiveness has been evaluated in phantoms and healthy volunteers and compared to conventional MP-RAGE acquisition. RESULTS: MP-RAGE and MP-RAVE anatomical images were rated "good" to "excellent" in overall image quality, with artifact level between "mild" and "no artifacts", and with no statistically significant difference between methods. During head motion, MP-RAVE showed higher inherent robustness with artifacts confined to local brain regions. In combination with motion correction, MP-RAVE provided noticeably improved image quality during different head motion and showed statistically significant improvement in image sharpness. CONCLUSION: MP-RAVE provides comparable image quality and contrast to conventional MP-RAGE with improved robustness to head motion. In combination with retrospective 3D motion correction, MP-RAVE can be a useful alternative to MP-RAGE, especially in non-cooperative or pediatric patients.

Time-dependent diffusivity and kurtosis in phantoms and patients with head and neck cancer.

PURPOSE: To assess the reliability of measuring diffusivity, diffusional kurtosis, and cellular-interstitial water exchange time with long diffusion times (100-800 ms) using stimulated-echo DWI. METHODS: Time-dependent diffusion MRI was tested on two well-established diffusion phantoms and in 5 patients with head and neck cancer. Measurements were conducted using an in-house diffusion-weighted STEAM-EPI pulse sequence with multiple diffusion times at a fixed TE on three scanners. We used the weighted linear least-squares fit method to estimate time-dependent diffusivity, D ( t ) $$ D(t) $$ , and diffusional kurtosis, K ( t ) $$ K(t) $$ . Additionally, the Kärger model was used to estimate cellular-interstitial water exchange time ( τ ex $$ {\tau}_{ex} $$ ) from K ( t ) $$ K(t) $$ . RESULTS: Diffusivity measured by time-dependent STEAM-EPI measurements and commercial SE-EPI showed comparable results with R2 above 0.98 and overall 5.4 ± 3.0% deviation across diffusion times. Diffusional kurtosis phantom data showed expected patterns: constant D $$ D $$ and K $$ K $$  = 0 for negative controls and slow varying D $$ D $$ and K $$ K $$ for samples made of nanoscopic vesicles. Time-dependent diffusion MRI in patients with head and neck cancer found that the Kärger model could be considered valid in 72% ± 23% of the voxels in the metastatic lymph nodes. The median cellular-interstitial water exchange time estimated for lesions was between 58.5 ms and 70.6 ms. CONCLUSIONS: Based on two well-established diffusion phantoms, we found that time-dependent diffusion MRI measurements can provide stable diffusion and kurtosis values over a wide range of diffusion times and across multiple MRI systems. Moreover, estimation of cellular-interstitial water exchange time can be achieved using the Kärger model for the metastatic lymph nodes in patients with head and neck cancer.

Case Report: Giant Thyroid Angiolipoma-Challenging Clinical Diagnosis and Novel Genetic Alterations.

BACKGROUND: A 64-year-old man presented with a 7.8 cm lipomatous thyroid mass discovered on magnetic resonance imaging. METHODS: After two non-diagnostic fine needle aspirations (FNAs) were performed, computed tomography (CT) revealed features concerning for malignancy including central necrosis and infiltrative borders. A third FNA was still non-diagnostic. Total thyroidectomy was performed. RESULTS: Upon pathologic examination, the final diagnosis was primary thyroid angiolipoma. The lesion contained central fat necrosis with ischemic features, attributable to the FNAs. CONCLUSION: Ours is the third published case report of this rare entity. To date, no lipomatous thyroid tumor has undergone extensive genomic testing. Next-generation sequencing of our case revealed multiple genetic alterations, supporting the concept of angiolipomas being true neoplasms. Whereas the two previously reported cases in the literature were radiographically much smaller and appeared indolent, the large tumor in our case exhibited radiographic features concerning for liposarcoma, which belied the benign final pathologic diagnosis. Our case demonstrates that conservative surgical management (partial thyroidectomy) may be considered for lipomatous thyroid tumors, with further interventions to be determined only after final pathologic diagnosis.

Stereotactic body radiation therapy for an unresectable FGF23-secreting tumor of the cervical spine: A case report and literature review.

We present the case of a 65-year-old male with tumor-induced osteomalacia (TIO) caused by an FGF23-secreting phosphaturic tumor of C2 treated definitively with stereotactic body radiation therapy (SBRT) and kyphoplasty. The patient exhibited notable reduction in FGF23 6 weeks following radiotherapy. He also received a dose of the FGF23 monoclonal antibody, burosumab. We discuss the case with emphasis on radiation in the management of TIO. This case demonstrates SBRT as a well-tolerated local treatment option for the management of unresectable FGF23-producing tumors.

Predictive Value of a Genomic Classifier in Indeterminate Thyroid Nodules Based on Nodule Size.

Importance: Genomic classifiers were developed to better guide clinicians in the treatment of indeterminate thyroid nodules (ITNs). To our knowledge, whether there is variation in the diagnostic accuracy of these tests depending on ITN size has not been previously studied. Objective: To analyze the diagnostic performance of a genomic classifier in relation to ITN size. Design, Setting, and Participants: A case series study with medical records review was conducted including all patients with a cytologic diagnosis of ITN managed with genomic classifier testing and surgery from January 2015 to December 2018 at NYU Langone Health. Demographics, ITN characteristics, genomic profiles, treatment, and final pathologic findings were recorded. Data analysis was conducted from March to April 2021. Main Outcomes and Measures: The primary aim was to assess the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of a genomic classifier test (ThyroSeq) in relation to ITN size (<2, 2-4, and >4 cm). The secondary aim was to investigate the risk of cancer associated with genetic signatures. Results: Of the 212 patients with 218 ITNs, 158 (74.5%) were women; median (SD) age was 49 (15.6) years. Genomic classifier results were positive in 173 ITNs (79.4%) treated with surgery. In this group of 173 positive ITNs, 46 (26.6%) were malignant on final pathologic testing. Overall, the observed cancer prevalence in the population was 23.9% (52 ITNs). In 45 ITNs that underwent surgery despite a negative genomic classifier interpretation, 6 (13.3%) were malignant. The PPV of a positive test was 27% and the NPV was 87%. The PPV and NPV findings improved as the ITN size increased (<2 cm [n = 98]: PPV, 25%; NPV, 79% vs >4 cm [n = 33]: PPV, 50%; NPV, 89%). Test specificity was higher in larger ITNs (<2 cm: 15% vs >4 cm: 40%; P = .01). Isolated RAS sequence variations were the most common variant identified in malignant nodules (11 [21.1%] of all ITNs), followed by BRAF variants (7 [13.5%] of all ITNs). Conclusions and Relevance: In this case series, the performance of the ThyroSeq test improved for larger ITNs. The risk of cancer in large ITNs with negative test results was low. These data suggest that, in genomic classifier-negative ITNs larger than 4 cm, initial management of thyroid lobectomy may be sufficient.

Delineation of Radiation Therapy Target Volumes for Lingual Nerve Involvement.

It is important for radiation oncologists to be able to accurately contour the lingual nerve pathway, as it is commonly involved in oral cavity cases. However, most atlases do not give a detailed account of the entire lingual nerve pathway as it traverses from the oral cavity, through the masticator space, to the base of the skull. Three experienced head and neck cancer specialists (two radiation oncologists and one neuroradiologist) examined anatomy textbooks, institutional magnetic resonance imaging (MRI), and computed tomography (CT) images of normal anatomy and also recurrences along the lingual nerve pathway to determine "anchor points" to help radiation oncologists contour more confidently. We found five anchor points to help radiation oncologists contour the lingual nerve pathway: At the level of the foramen ovale, the lateral pterygoid, the transition between lateral and medial pterygoid, the medial pterygoid (within the pterygomandibular space), and the oral cavity. Five anchor points with easily identifiable anatomy are established that radiation oncologists can use to contour the lingual nerve pathway more confidently.

Tumor-Induced Osteomalacia Localized and Excised After Pregnancy.

OBJECTIVE: Tumor-induced osteomalacia (TIO) is a rare osteomalacia characterized by paraneoplastic secretion of fibroblast growth factor 23. Concomitant occurrence of TIO during pregnancy is rarer still. Our objective was to report a young patient with debilitating fractures diagnosed with TIO who became pregnant and subsequently had her tumor localized by gallium-68 (Ga-68) DOTATATE positron emission tomography/magnetic resonance imaging (PET/MRI). CASE REPORT: A 28 year-old woman with a 2-year history of stress fractures was found to have the following: (1) alkaline phosphatase level, 220 (reference range, 30-95) U/L; (2) phosphorus level, 2.1 (2.5-5.0) mg/dL; (3) 1,25-dihydroxyvitamin D3 level, <8 (18-72) pg/mL; (4) 24-hour urine phosphorus level, 0.5 (0.3-1.3) g; and (5) fibroblast growth factor 23 levels, 1241 (reference range, <180) RU/mL. The patient became pregnant, and at term, a cesarean delivery was performed. Ga-68 DOTATATE PET/MRI showed a 9-mm intracortical mass in the right fibular head and right femoral and bilateral calcaneal stress fractures. The fibular lesion was resected; pathology showed a 1.5-cm lesion with positive fibroblast growth factor receptor 1 staining. DISCUSSION: This patient with TIO had an uneventful pregnancy and delivery. TIO is typically caused by benign mesenchymal tumors. Ga-68 DOTATATE PET/computed tomography has been used for localizing tumors causing TIO, yet MRI has superior contrast resolution over computed tomography. Therefore, it is not surprising that Ga-68 PET/MRI successfully localized this patient's tumor to the intracortical space of the fibular head and distinguished it from insufficiency fractures. CONCLUSION: To our knowledge, this is the first report of phosphate treatment in a pregnant patient with TIO and the first report of a tumor-inducing TIO being localized by Ga-68 DOTATATE PET/MRI.

Growth hormone secreting pituitary carcinomas: Case report and review of literature.

OBJECTIVE: Pituitary carcinoma is a rare tumor, defined as a tumor of adenohypophyseal cells with systemic or craniospinal metastasis. We present a case of a growth hormone (GH)-secreting pituitary carcinoma with a review of literature to better characterize this disease. DESIGN: Case report and literature review of 25 cases of GH-secreting pituitary carcinomas RESULTS: The age of diagnosis of GH-secreting carcinomas ranged 24-69 years old with a mean age of 44.4 with 52% of cases present in females. Mean latency period between diagnosis of acromegaly and transition to pituitary carcinoma was 11.4 years with mean survival being 3.4 years. CONCLUSION: Growth hormone (GH)-secreting pituitary carcinomas are rare and hard to distinguish from aggressive pituitary adenomas. From review of literature, treatment options include debulking surgery, radiotherapy, or chemotherapy with dismal outcomes. There are no diagnostic markers or features which can predict metastatic progression of these tumors. Future studies with genomic landscapes and relevant tumor markers are needed to identify pituitary tumors most likely to metastasize.

[68Ga]-DOTATATE PET/MRI in the diagnosis and management of recurrent head and neck paraganglioma with spinal metastasis.

Most head and neck paragangliomas (PGLs) are biochemically silent and often present with recurrence and metastases in association with hereditary syndromes. Whole-body functional imaging is increasingly used to detect tumor extent and guide treatment planning of PGLs. [68Ga]-DOTATATE, which targets somatostatin receptor 2 (SSTR2) overexpression, has emerged as a sensitive functional imaging modality in PGLs. We present a patient with metastatic glomus caroticum PGL in whom [68Ga]-DOTATATE PET/MRI provided a more accurate characterization of metastatic extent, as compared to gadolinium-enhanced MRI of the neck and whole body [18F]-FDG PET/CT. We then review the current literature and discuss the imaging implications of [68Ga]-DOTATATE PET/MRI in PGLs.

Imaging for Metastatic Renal Cell Carcinoma.

Patients with renal cell carcinoma may develop metastases after radical nephrectomy, and therefore monitoring with imaging for recurrent or metastatic disease is critical. Imaging varies with specific suspected site of disease. Computed tomography/MRI of the abdomen and pelvis are mainstay modalities. Osseous and central nervous system imaging is reserved for symptomatic patients. Radiologic reporting is evolving to reflect effects of systemic therapy on lesion morphology. Nuclear medicine studies compliment routine imaging as newer agents are evaluated for more accurate tumor staging. Imaging research aims to fill gaps in treatment selection and monitoring of treatment response in metastatic renal cell carcinoma.

Cavernous sinus lesions.

The cavernous sinus is a complex structure susceptible to a wide variety of vascular, neoplastic and inflammatory pathologies. Vascular pathologies include ICA aneurysms, carotid-cavernous fistulas, cavernous sinus thrombosis, and cavernous hemangioma. Neoplasms that involve the cavernous sinus include pituitary adenoma, meningioma, schwannoma, lymphoma, perineural tumor spread, metastases, and direct tumor invasion. Infectious and inflammatory diseases include Tolosa-Hunt syndrome, sarcoidosis, granulomatosis with polyangiitis, IgG-4 related disease and invasive fungal infections. In this article, we review the clinical and imaging findings of a number of pathologies involving the cavernous sinus, focusing on key features that can narrow the differential diagnosis and, in some cases, support a particular diagnosis.

COVID-19-associated Diffuse Leukoencephalopathy and Microhemorrhages.

Diffuse leukoencephalopathy and juxtacortical and/or callosal microhemorrhages were brain imaging features in critically ill patients with coronavirus disease 2019. Coronavirus disease 2019 (COVID-19) has been reported in association with a variety of brain imaging findings such as ischemic infarct, hemorrhage, and acute hemorrhagic necrotizing encephalopathy. Herein, the authors report brain imaging features in 11 critically ill patients with COVID-19 with persistently diminished mental status who underwent MRI between April 5 and April 25, 2020. These imaging features include (a) confluent T2 hyperintensity and mild restricted diffusion in bilateral supratentorial deep and subcortical white matter (in 10 of 11 patients) and (b) multiple punctate microhemorrhages in juxtacortical and callosal white matter (in seven of 11 patients). The authors also discuss potential pathogeneses.

Endoscopic Visualization of the True Maxillary Ostium Following Uncinectomy.

OBJECTIVES: To examine the frequency in which angled endoscopes are necessary to visualize the true maxillary ostium (TMO) following uncinectomy and prior to maxillary antrostomy. Additionally, to identify preoperative computed tomography (CT) measures that predict need for an angled endoscope to visualize the TMO. STUDY DESIGN: Retrospective study. SETTING: Tertiary academic hospital. PATIENTS AND METHODS: Patients who underwent endoscopic sinus surgery (ESS) between December of 2017 and August of 2018 were retrospectively identified. Cases were reviewed if they were primary ESS cases for chronic rhinosinusitis without polyposis and if they were at least 18 years of age. RESULTS: Sixty-three maxillary antrostomies were reviewed (82.5% were from bilateral cases). Thirty-five cases (55.6%) required an angled endoscope in order to visualize the TMO. Of the preoperative CT measures examined, a smaller sphenoid keel-caudal septum-nasolacrimal duct (SK-CS-NL) angle was significantly associated with need for an angled endoscope intraoperatively to visualize the TMO (17.1° SD ± 3.2 vs 15.0° SD ± 2.9; P = .010). CONCLUSION: Angled endoscopes are likely required in the majority of maxillary antrostomies to visualize the TMO. This is important to recognize in order to prevent iatrogenic recirculation. The SK-CS-NL angle may help to identify cases preoperatively which require an angled endoscope to identify the TMO during surgery.