Publications

2023

Kesner, Adam L, Lukas M Carter, Juan C Ocampo Ramos, Daniel Lafontaine, Edmond A Olguin, Justin L Brown, Bonnie President, Derek W Jokisch, Darrell R Fisher, and Wesley E Bolch. (2023) 2023. “MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.”. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine 64 (7): 1117-24. https://doi.org/10.2967/jnumed.122.264225.

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging.

Christinaki, Anastasia C, Bart Theelen, Alkmini Zania, Selene Dall’ Acqua Coutinho, Javier F Cabañes, Teun Boekhout, and Vassili N Kouvelis. (2023) 2023. “Co-Evolution of Large Inverted Repeats and G-Quadruplex DNA in Fungal Mitochondria May Facilitate Mitogenome Stability: The Case of Malassezia.”. Scientific Reports 13 (1): 6308. https://doi.org/10.1038/s41598-023-33486-4.

Mitogenomes are essential due to their contribution to cell respiration. Recently they have also been implicated in fungal pathogenicity mechanisms. Members of the basidiomycetous yeast genus Malassezia are an important fungal component of the human skin microbiome, linked to various skin diseases, bloodstream infections, and they are increasingly implicated in gut diseases and certain cancers. In this study, the comparative analysis of Malassezia mitogenomes contributed to phylogenetic tree construction for all species. The mitogenomes presented significant size and gene order diversity which correlates to their phylogeny. Most importantly, they showed the inclusion of large inverted repeats (LIRs) and G-quadruplex (G4) DNA elements, rendering Malassezia mitogenomes a valuable test case for elucidating the evolutionary mechanisms responsible for this genome diversity. Both LIRs and G4s coexist and convergently evolved to provide genome stability through recombination. This mechanism is common in chloroplasts but, hitherto, rarely found in mitogenomes.

Bezuidenhout, Abraham F, Pei-Kang Wei, Deborah Burstein, Alexander Brook, Olga R Brook, Steven D Freedman, and Leo L Tsai. (2023) 2023. “Unexplained Acute Distal Pancreatitis: Association With Subsequent Diagnosis of Pancreatic Cancer.”. AJR. American Journal of Roentgenology 221 (2): 196-205. https://doi.org/10.2214/AJR.23.28999.

BACKGROUND. Distal pancreatitis is an atypical imaging subtype of acute pancreatitis involving only the pancreatic body and tail, the head being spared. If no cause is identified, suspicion of a small imaging-occult cancer may be warranted. OBJECTIVE. The purpose of this study was to determine the frequency of subsequently diagnosed pancreatic cancer in patients with unexplained acute distal pancreatitis and to compare this frequency to that found in patients with unexplained nondistal pancreatitis. METHODS. This retrospective study included patients who underwent contrast-enhanced CT between January 1, 2019, and December 31, 2020, that showed acute pancreatitis without identifiable explanation. Studies were classified as showing distal or nondistal acute pancreatitis on the basis of consensus. The Fisher exact test was used to compare the frequency of subsequent histologic diagnosis of pancreatic cancer between groups. Negative classification required 6 or more months of imaging follow-up and/or 12 or more months of clinical follow-up. Interreader agreement among seven readers of varying experience was assessed by Fleiss kappa. RESULTS. Among 215 patients with acute pancreatitis, 116 (54%) had no identifiable explanation and formed the study sample. A total of 100 of 116 (86%) patients (59 men, 41 women; mean age, 57 ± 18 [SD] years) had nondistal acute pancreatitis; 16 of 116 (14%) patients (10 men, six women; mean age, 66 ± 14 years) had distal acute pancreatitis. Among patients with nondistal pancreatitis, none were subsequently diagnosed with pancreatic cancer; 62 had sufficient follow-up (median, 2.5 years) to be classified as having negative follow-up for pancreatic cancer. Among patients with distal pancreatitis, nine were subsequently diagnosed with pancreatic cancer (median interval to suspected cancer on subsequent CT, 174 days); five had sufficient follow-up (median, 3.1 years) to be classified as having negative follow-up for pancreatic cancer. The frequency of pancreatic cancer was higher (p < .001) in patients with distal pancreatitis (9/14 [64%; 95% CI, 35-87%]) than in with those with nondistal pancreatitis (0/62 [0%; 95% CI, 0-6%]). Interreader agreement on classification of distal versus nondistal pancreatitis was almost perfect (κ = 0.81). CONCLUSION. Distal pancreatitis without identifiable cause on CT is an uncommon but unique imaging subtype of acute pancreatitis that is associated with a high frequency of pancreatic cancer. CLINICAL IMPACT. In patients with acute distal pancreatitis without identifiable cause, endoscopic ultrasound-guided biopsy should be considered to evaluate for an underlying small cancer.

Liu, Guoyu, Runqi Zhang, Sen Li, Rehmat Ullah, Fengping Yang, Zihao Wang, Weilong Guo, et al. (2023) 2023. “TaMADS29 Interacts With TaNF-YB1 to Synergistically Regulate Early Grain Development in Bread Wheat.”. Science China. Life Sciences 66 (7): 1647-64. https://doi.org/10.1007/s11427-022-2286-0.

Grain development is a crucial determinant of yield and quality in bread wheat (Triticum aestivum L.). However, the regulatory mechanisms underlying wheat grain development remain elusive. Here we report how TaMADS29 interacts with TaNF-YB1 to synergistically regulate early grain development in bread wheat. The tamads29 mutants generated by CRISPR/Cas9 exhibited severe grain filling deficiency, coupled with excessive accumulation of reactive oxygen species (ROS) and abnormal programmed cell death that occurred in early developing grains, while overexpression of TaMADS29 increased grain width and 1,000-kernel weight. Further analysis revealed that TaMADS29 interacted directly with TaNF-YB1; null mutation in TaNF-YB1 caused grain developmental deficiency similar to tamads29 mutants. The regulatory complex composed of TaMADS29 and TaNF-YB1 exercises its possible function that inhibits the excessive accumulation of ROS by regulating the genes involved in chloroplast development and photosynthesis in early developing wheat grains and prevents nucellar projection degradation and endosperm cell death, facilitating transportation of nutrients into the endosperm and wholly filling of developing grains. Collectively, our work not only discloses the molecular mechanism of MADS-box and NF-Y TFs in facilitating bread wheat grain development, but also indicates that caryopsis chloroplast might be a central regulator of grain development rather than merely a photosynthesis organelle. More importantly, our work offers an innovative way to breed high-yield wheat cultivars by controlling the ROS level in developing grains.

Dave, Priya, Olga R Brook, Alexander Brook, Ammar Sarwar, and Bettina Siewert. (2023) 2023. “Moral Distress in Radiology: Frequency, Root Causes, and Countermeasures-Results of a National Survey.”. AJR. American Journal of Roentgenology 221 (2): 249-57. https://doi.org/10.2214/AJR.22.28968.

BACKGROUND. A major cause of burnout is moral distress: when one knows the right course of action but institutional constraints make the right course impossible to pursue. OBJECTIVE. The purpose of this study was to assess the frequency and severity with which radiologists experience moral distress and to explore moral distress's root causes and countermeasures. METHODS. This study entailed a national survey that evaluated moral distress in radiology. The survey incorporated the validated Moral Distress Scale for Health Care Professionals, along with additional questions. After the scale was modified for applicability to radiology, respondents were asked to assess 16 clinical scenarios in terms of frequency and severity of moral distress. On May 10, 2022, the survey was sent by e-mail to 425 members of radiology practices included on a national radiology society's quality-and-safety LISTSERV. The Measure of Moral Distress for Health Care Professionals (MMD-HP) score was calculated for each respondent as a summary measure of distress across scenarios (maximum possible score, 256). RESULTS. After 12 surveys with incomplete data were excluded, the final analysis included 93 of 425 respondents (22%). A total of 91 of 93 respondents (98%) experienced at least some moral distress for at least one scenario. A total of 17 of 93 respondents (18%) had left a clinical position due to moral distress; 26 of 93 (28%) had considered leaving a clinical position due to moral distress but did not leave. The mean MMD-HP score was 73 ± 51 (SD) for those who had left, 89 ± 47 for those who had considered leaving but did not leave, and 39 ± 35 for those who had never considered leaving (p < .001). A total of 41 of 85 respondents (48%) thought that the COVID-19 pandemic had influenced their moral distress level. Across respondents, the three scenarios with highest moral distress were related to systemic causes (higher case volume than could be read safely, high case volume preventing teaching residents, and lack of administrative action or support). The countermeasure most commonly selected to alleviate moral distress was educating leadership about sources of moral distress (71%). CONCLUSION. Moral distress is prevalent in radiology, typically relates to systemic causes, and is a reported contributor to radiologists changing jobs. CLINICAL IMPACT. Urgent action by radiology practice leadership is required to address moral distress, as radiologists commonly practice in environments contradictory to their core values as physicians.

Rhew, Kiyon, Jisu Choi, Kyungim Kim, Kyung Hee Choi, So-Hee Lee, and Heung-Woo Park. (2023) 2023. “Increased Risk of Anemia in Patients With Asthma.”. Clinical Epidemiology 15: 31-38. https://doi.org/10.2147/CLEP.S394717.

PURPOSE: Asthma can cause a systemic inflammatory response, and anemia of chronic disease (ACD) is known to be caused by other disorders with a chronic inflammatory state. However, it is unclear whether the incidence of anemia is increased in patients with asthma. The objective of this study was to compare the incidence of anemia in patients with asthma and healthy adults.

PATIENTS AND METHODS: This retrospective cohort study included patients newly diagnosed with asthma at Seoul National University Hospital from 2010 to 2017. Patients with comorbidities before the first visit (index date) that may increase anemia risk were excluded. Cox regression models adjusting for patient age, sex, and obesity were used to compare anemia hazard ratios (HRs) between asthma patients (n=1354) and healthy adults (n=1731).

RESULTS: This study included 3085 patients. During 5-y follow-up, anemia occurred in 203 (15.0%) patients with asthma and 79 (4.6%) healthy adults. Compared with healthy adults, the HR for anemia after adjusting for age, sex, and obesity was 4.06 (95% CI: 2.70-6.09) in patients with asthma. In patients aged 18-64.9 y, the adjusted HR of anemia was 3.27 (95% CI: 2.12-5.04) in patients with asthma, compared to healthy patients. In patients >65 y, this adjusted HR was 5.56 (95% CI: 1.31-23.67).

CONCLUSION: The risk of anemia was increased in patients with asthma after adjusting for sex, age, and obesity and excluding comorbidities that can cause anemia. These results suggest the need for regular monitoring for anemia in patients with asthma.

Santagata, Mario, Salvatore D’Amato, Ivo Ferrieri, Annalisa Pollice, Pasquale Verolino, Ciro Emiliano Boschetti, and Gianpaolo Tartaro. (2023) 2023. “A Modified of Bilateral Sagittal Split Osteotomy: Technical Note and Proposal of a Nomenclature on the Osteotomy Lines.”. The Journal of Craniofacial Surgery 34 (3): e306-e308. https://doi.org/10.1097/SCS.0000000000009251.

Bilateral sagittal split osteotomy for orthognathic surgery is the most used technique for mandible advancement or setback and has been well documented and modified over the years since Trauner and Obwegeser described it. The improvement brought by each technique allowed the surgeons to perform safer osteotomies, shorten the operative time, and increased the flexibility of the programmed mandibular movements. The authors present a modification of the bilateral sagittal osteotomy technique with the aim of making the technique easier to perform and more comfortable for the surgeon for the purpose of positioning the osteosynthesis plates and screws. Finally, the authors describe a nomenclature on the osteotomy lines of the bilateral sagittal split osteotomy.

Friedman, Rosie, Clarissa Lee, JacqueLyn R Kinney, Betsa Parsai Salehi, Geunwon Kim, Dhruv Singhal, and Leo L Tsai. (2023) 2023. “Fluid Distribution Patterns in Early-Stage Upper Extremity Lymphedema.”. Annals of Plastic Surgery 90 (6S Suppl 5): S622-S625. https://doi.org/10.1097/SAP.0000000000003494.

INTRODUCTION: Magnetic resonance imaging (MRI) stage 1 (early stage) upper extremity lymphedema is characterized by fluid infiltration in the subcutaneous tissues that does not exceed 50% of the extremity circumference at any level. The spatial fluid distribution in these cases has not been detailed and may be important to help determine the presence and location of compensatory lymphatic channels. The aim of this study is to determine whether there was a pattern of distribution of fluid infiltration in patients with early-stage lymphedema that could correspond to known lymphatic pathways in the upper extremity.

METHODS: A retrospective review identified all patients with MRI stage 1 upper extremity lymphedema who were evaluated at a single lymphatic center. Using a standardized scoring system, a radiologist graded the severity of fluid infiltration at 18 anatomical locations. A cumulative spatial histogram was then created to map out regions where fluid accumulation occurred most and least frequently.

RESULTS: Eleven patients with MRI stage 1 upper extremity lymphedema were identified between January 2017 and January 2022. The mean age was 58 years and the mean BMI was 30 m/kg2. One patient had primary lymphedema and the remaining 10 had secondary lymphedema. The forearm was affected in nine cases, and fluid infiltration was predominantly concentrated along the ulnar aspect, followed by the volar aspect, while the radial aspect was completely spared. Within the upper arm, fluid was primarily concentrated distally and posteriorly, and occasionally medially.

CONCLUSIONS: In patients with early-stage lymphedema, fluid infiltration is concentrated along the ulnar forearm and the posterior distal upper arm, which aligns with the tricipital lymphatic pathway. There is also sparing of fluid accumulation along the radial forearm in these patients, suggesting a more robust lymphatic drainage along this region, possibly due to a connection to the lateral upper arm pathway.

Alsop, David C, Ece Ercan, Olivier M Girard, Alex L Mackay, Carl A Michal, Gopal Varma, Elena Vinogradov, and Guillaume Duhamel. (2023) 2023. “Inhomogeneous Magnetization Transfer Imaging: Concepts and Directions for Further Development.”. NMR in Biomedicine 36 (6): e4808. https://doi.org/10.1002/nbm.4808.

Off-resonance radio frequency irradiation can induce the ordering of proton spins in the dipolar fields of their neighbors, in molecules with restricted mobility. This dipolar order decays with a characteristic relaxation time, T1D , that is very different from the T1 and T2 relaxation of the nuclear alignment with the main magnetic field. Inhomogeneous magnetization transfer (ihMT) imaging is a refinement of magnetization transfer (MT) imaging that isolates the MT signal dependence on dipolar order relaxation times within motion-constrained molecules. Because T1D relaxation is a unique contrast mechanism, ihMT may enable improved characterization of tissue. Initial work has stressed the high correlation between ihMT signal and myelin density. Dipolar order relaxation appears to be much longer in membrane lipids than other molecules. Recent work has shown, however, that ihMT acquisitions may also be adjusted to emphasize different ranges of T1D . These newer approaches may be sensitive to other microstructural components of tissue. Here, we review the concepts and history of ihMT and outline the requirements for further development to realize its full potential.

Lakhman, Yulia, Emily A Aherne, Vetri Sudar Jayaprakasam, Stephanie Nougaret, and Caroline Reinhold. (2023) 2023. “Staging of Cervical Cancer: A Practical Approach Using MRI and FDG PET.”. AJR. American Journal of Roentgenology 221 (5): 633-48. https://doi.org/10.2214/AJR.23.29003.

This review provides a practical approach to the imaging evaluation of patients with cervical cancer (CC), from initial diagnosis to restaging of recurrence, focusing on MRI and FDG PET. The primary updates to the International Federation of Gynecology and Obstetrics (FIGO) CC staging system, as well as these updates' relevance to clinical management, are discussed. The recent literature investigating the role of MRI and FDG PET in CC staging and image-guided brachytherapy is summarized. The utility of MRI and FDG PET in response assessment and posttreatment surveillance is described. Important findings on MRI and FDG PET that interpreting radiologists should recognize and report are illustrated. The essential elements of structured reports during various phases of CC management are outlined. Special considerations, including the role of imaging in patients desiring fertility-sparing management, differentiation of CC and endometrial cancer, and unusual CC histologies, are also described. Finally, future research directions including PET/MRI, novel PET tracers, and artificial intelligence applications are highlighted.