Quantitative myocardial T2 mapping adds value to Japanese circulation society diagnostic criteria for active cardiac sarcoidosis.

Noninvasive identification of active myocardial inflammation in patients with cardiac sarcoidosis plays a key role in management but remains elusive. T2 mapping is a proposed solution, but the added value of quantitative myocardial T2 mapping for active cardiac sarcoidosis is unknown. Retrospective cohort analysis of 56 sequential patients with biopsy-confirmed extracardiac sarcoidosis who underwent cardiac MRI for myocardial T2 mapping. The presence or absence of active myocardial inflammation in patients with CS was defined using a modified Japanese circulation society criteria within one month of MRI. Myocardial T2 values were obtained for the 16 standard American Heart Association left ventricular segments. The best model was selected using logistic regression. Receiver operating characteristic curves and dominance analysis were used to evaluate the diagnostic performance and variable importance. Of the 56 sarcoidosis patients included, 14 met criteria for active myocardial inflammation. Mean basal T2 value was the best performing model for the diagnosis of active myocardial inflammation in CS patients (pR2 = 0.493, AUC = 0.918, 95% CI 0.835-1). Mean basal T2 value > 50.8 ms was the most accurate threshold (accuracy = 0.911). Mean basal T2 value + JCS criteria was significantly more accurate than JCS criteria alone (AUC = 0.981 vs. 0.887, p = 0.017). Quantitative regional T2 values are independent predictors of active myocardial inflammation in CS and may add additional discriminatory capability to JCS criteria for active disease.

Fiber Ball White Matter Modeling Reveals Microstructural Alterations in Healthy Brain Aging.

Age-related white matter degeneration is characterized by myelin breakdown and neuronal fiber loss that preferentially occur in regions that myelinate later in development. Conventional diffusion MRI (dMRI) has demonstrated age-related increases in diffusivity but provide limited information regarding the tissue-specific changes driving these effects. A recently developed dMRI biophysical modeling technique, Fiber Ball White Matter (FBWM) modeling, offers enhanced biological interpretability by estimating microstructural properties specific to the intra-axonal and extra-axonal spaces. We used FBWM to illustrate the biological mechanisms underlying changes throughout white matter in healthy aging using data from 63 cognitively unimpaired adults ages 45-85 with no radiological evidence of neurodegeneration or incipient Alzheimer's disease. Conventional dMRI and FBWM metrics were computed for two late-myelinating (genu of the corpus callosum and association tracts) and two early-myelinating regions (splenium of the corpus callosum and projection tracts). We examined the associations between age and these metrics in each region and tested whether age was differentially associated with these metrics in late- vs. early-myelinating regions. We found that conventional metrics replicated patterns of age-related increases in diffusivity in late-myelinating regions. FBWM additionally revealed specific intra- and extra-axonal changes suggestive of myelin breakdown and preferential loss of smaller-diameter axons, yielding in vivo corroboration of findings from histopathological studies of aged brains. These results demonstrate that advanced biophysical modeling approaches, such as FBWM, offer novel information about the microstructure-specific alterations contributing to white matter changes in healthy aging. These tools hold promise as sensitive indicators of early pathological changes related to neurodegenerative disease.

Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease.

OBJECTIVE: The Alzheimer's continuum is biologically defined by beta-amyloid deposition, which at the earliest stages is superimposed upon white matter degeneration in aging. However, the extent to which these co-occurring changes is characterized is relatively underexplored. The goal of this study was to use diffusional kurtosis imaging (DKI) and biophysical modeling to detect and describe amyloid-related white matter changes in preclinical Alzheimer disease. METHODS: Cognitively unimpaired participants ages 45 to 85 years completed brain magnetic resonance imaging, amyloid positron emission tomography (florbetapir), neuropsychological testing, and other clinical measures at baseline in a cohort study. We tested whether beta-amyloid-negative (AB-) and -positive (AB+) participants differed on DKI-based conventional (ie, fractional anisotropy [FA], mean diffusivity [MD], mean kurtosis) and modeling (ie, axonal water fraction [AWF], extra-axonal radial diffusivity [De,⊥ ]) metrics, and whether these metrics were associated with other biomarkers. RESULTS: We found significantly greater diffusion restriction (higher FA/AWF, lower MD/De,⊥ ) in white matter in AB+ than AB- (partial η2 =0.08-0.19), more notably in the extra-axonal space within primarily late myelinating tracts. Diffusion metrics predicted amyloid status incrementally over age (area under the curve = 0.84) with modest yet selective associations, where AWF (a marker of axonal density) correlated with speed/executive functions and neurodegeneration, whereas De,⊥ (a marker of gliosis/myelin repair) correlated with amyloid deposition and white matter hyperintensity volume. INTERPRETATION: These results support prior evidence of a nonmonotonic change in diffusion behavior, where an early increase in diffusion restriction is hypothesized to reflect inflammation and myelin repair prior to an ensuing decrease in diffusion restriction, indicating glial and neuronal degeneration. ANN NEUROL 2022;91:864-877.

Unusual Radiotracer Deposition to the Forearm After Intrahepatic Injection of 99mTc-Macroaggregated Albumin Using a Transradial Approach.

ABSTRACT: Arterial mapping and 99mTc-macroaggregated albumin (99mTc-MAA) hepatic perfusion imaging are routinely performed before 90Y radioembolization of hepatic tumors. These procedures serve multiple purposes, including an anatomical survey of hepatic arterial anatomy, interrogating expected microsphere distribution to avoid nontargeted embolization during therapy, and evaluating for possible hepatopulmonary shunting. We present a case where 99mTc-MAA planar images revealed unexpected soft tissue uptake within the left forearm, an unexpected complication that may result from residual 99mTc-MAA in the catheter being expelled as the catheter is removed, which is particularly important to avoid during the 90Y radioembolization procedure given the risk for associated radionecrosis.

Utility of Dynamic Hepatobiliary Scintigraphy in Identifying a Duct of Luschka Bile Leak.

ABSTRACT: Hepatobiliary scintigraphy is a sensitive tool for the detection of a suspected bile leak following cholecystectomy. Traditionally, it has been used to identify, but not localize the source of the leak. Herein we present a case of a bile leak related to a duct of Luschka injury that was identified on dynamic hepatobiliary scintigraphy, but was less evident on a concurrently acquired MRI. This case highlights the scintigraphic features of a bile leak from an accessory duct and underscores the importance of reviewing early dynamic images to potentially identify the source of a leak.

Risk of Radiation Exposure to Clinical Staff from Paracenteses of Large-Volume Chylous Ascites After 177Lu-DOTATATE Infusion.

177Lu-DOTATATE has gained wide clinical acceptance for the treatment of advanced gastroenteropancreatic neuroendocrine tumors; however, little is known regarding its accumulation in ascites. As such, clinical staff performing paracenteses shortly after a treatment dose may be concerned about their potential radiation exposure or the risk of contamination. Methods: In this report, therapeutic paracenteses were performed on a patient with metastatic intestinal carcinoid complicated by recurrent chylous ascites at various time intervals after a standard 7.4 GBq dose of 177Lu-DOTATATE. Samples of the fluid were analyzed in a scintillation counter to estimate the concentration of radioactivity. Results: The concentration of activity in the ascitic fluid obtained 3 d after an infusion was exceptionally low (175.3 ± 25.9 Bq/mL). Conclusion: Our findings suggest that paracenteses conducted as soon as 3 d after a standard dose of 177Lu-DOTATATE pose little to no risk in terms of radiation safety to staff performing the procedure.

Incidental Serous Cystadenoma Presenting as a Photopenic Pancreatic Defect on 18F-Fluciclovine PET/CT.

ABSTRACT: 18F-fluciclovine (Axumin) PET/CT has been widely used for the evaluation of biochemically recurrent prostate cancer following prior treatment. While lymph node and visceral organ metastases typically show increased radiotracer uptake, altered patterns of normal physiologic activity may also provide insight into other disease processes. We present a case of an incidental pancreatic head mass presenting as a photopenic defect on a staging 18F-fluciclovine PET/CT, which was subsequently confirmed to be a benign serous cystadenoma using multisequence MRI.

Terminal ileal micro-perforation from an ingested fish bone incidentally diagnosed with 111In-leukocyte scintigraphy in an asymptomatic patient.

111In-leukocyte scintigraphy has generally been considered a sensitive diagnostic test for the evaluation of infectious or inflammatory processes in the abdomen due to a lack of normal physiologic bowel activity. Herein we present a case of a patient status post endovascular repair of an abdominal aortic aneurysm for which an 111In-leukocyte scan was ordered to assess for graft infection. Planar imaging revealed an abnormal focus of radiotracer activity in the right lower quadrant of the abdomen. A SPECT-CT obtained to further delineate the anatomic location of abnormal activity showed abnormal leukocyte activity localizing to the terminal ileum secondary to a micro-perforation from an ingested fishbone. This case underscores the principle that in the absence of known intra-abdominal pathology, 111In-leukocyte activity in the abdomen should always be considered abnormal, and that further evaluation with dedicated cross-sectional imaging should be performed to assist with the localization of abnormal activity.

Scapulothoracic Articulation Disorders on 99mTc-MDP Bone Scintigraphy.

ABSTRACT: Disorders of the scapulothoracic articulation can cause significant pain, as well as an audible "snapping" or crepitus in advanced cases. Although radiography, CT, and MRI are used in the diagnosis of these conditions, little is known about their manifestations on nuclear imaging. We present a case of symmetric uptake at the inferior scapulothoracic articulations mimicking metastatic disease on a staging bone scan. Recognition of this pattern of activity is not only important to accurately exclude malignancy, but also to aid referring providers in addressing potential causes of patient morbidity.

Prospective Evaluation of the First Integrated Positron Emission Tomography/Dual-Energy Computed Tomography System in Patients With Lung Cancer.

PURPOSE: The aim of this pilot study was to prospectively evaluate the first integrated positron emission tomography (PET)/dual-energy computed tomography (DECT) system performance in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this single-center, prospective trial, consecutive patients with NSCLC referred for a PET study between May 2017 and June 2018 were enrolled. All patients received contrast-enhanced imaging on a clinical PET/DECT system. Data analysis included PET-based standard uptake values (SUVmax) and DECT-based iodine densities of tumor masses, lymph nodes, and distant metastases. Results were analyzed using correlation tests and receiver operating characteristics curves. RESULTS: The study population was composed of 21 patients (median age 62 y, 14 male patients). A moderate positive correlation was found between iodine density values (2.2 mg/mL) and SUVmax (10.5) in tumor masses (ρ=0.53, P<0.01). Iodine density values (2.3 mg/mL) and SUVmax (5.4) of lymph node metastases showed a weak positive correlation (ρ=0.23, P=0.14). In addition, iodine quantification analysis provided no added value in differentiating between pathologic and nonpathologic lymph nodes with an area under the curve (AUC) of 0.55 using PET-based SUVmax as the reference standard. A weak positive correlation was observed between iodine density (2.2 mg/mL) and SUVmax in distant metastases (14.9, ρ=0.23, P=0.52). CONCLUSIONS: The application of an integrated PET/DECT system in lung cancer might provide additional insights in the assessment of tumor masses. However, the added value of iodine density quantification for the evaluation of lymph nodes and distant metastases seems limited.

Antiseptic-Mediated Colloid Labeling as a Potential Source of Abnormal Liver and Spleen Uptake with 99mTc-Dimercaptosuccinic Acid.

Altered biodistribution can be a source of diagnostic error in the interpretation of nuclear medicine studies. This case reports an instance of increased liver and spleen uptake with 99mTc-dimercaptosuccinic acid believed to be a result of chlorhexidine-mediated colloid labeling. This finding underscores the principle that certain constituents of antiseptics may adversely affect the purity of radiopharmaceuticals during their preparation.

What is the preferred strength setting of the sinogram-affirmed iterative reconstruction algorithm in abdominal CT imaging?

Our primary objective in this study was to determine the preferred strength setting for the sinogram-affirmed iterative reconstruction algorithm (SAFIRE) in abdominal computed tomography (CT) imaging. Sixteen consecutive clinical CT scans of the abdomen were reconstructed by use of traditional filtered back projection (FBP) and 5 SAFIRE strengths: S1-S5. Six readers of differing experience were asked to rank the images on preference for overall diagnostic quality. The contrast-to-noise ratio was not significantly different between SAFIRE S1 and FBP, but increased with increasing SAFIRE strength. For pooled data, S2 and S3 were preferred equally but both were preferred over all other reconstructions. S5 was the least preferred, with FBP the next least preferred. This represents a marked disparity between the image quality based on quantitative parameters and qualitative preference. Care should be taken to factor in qualitative in addition to quantitative aspects of image quality when one is optimizing iterative reconstruction images.

Physician preference between low-dose computed tomography with a sinogram-affirmed iterative reconstruction algorithm and routine-dose computed tomography with filtered back projection in abdominopelvic imaging.

OBJECTIVE: The aim of this study was to directly compare the preference between low-dose sinogram-affirmed iterative reconstruction (SAFIRE) and routine filtered back projection (FBP) abdominopelvic computed tomography (CT). METHODS: A retrospective review identified 41 subjects who had undergone 2 different CT examinations at different times (a CT with reduced radiation dose SAFIRE and also a CT with routine-dose FBP). Radiation dose, patient size, and image noise were recorded. Two independent readers assessed the paired CT studies for preference in image quality in regard to 3 clinically relevant diagnostic endpoints (bowel pathology, biliary pathology, and general purpose). RESULTS: Radiation dose was significantly lower for SAFIRE (mean, 7.6 mGy; range, 4.1-15.4 mGy) than FBP (12.9 mGy; 6.7-31.6 mGy) (P < 0.001). Sinogram-affirmed iterative reconstruction was preferred for the general purpose and bowel evaluations, particularly when the level of radiation dose reduction was less than 33%. The preference for interpretation of the biliary system was equivocal, especially when the level of radiation reduction was increased greater than 33%. Filtered back projection was preferred when SAFIRE had a radiation reduction from FBP of greater than 50%. CONCLUSIONS: For abdominopelvic CT, low-dose CT with SAFIRE may produce preferred image quality over FBP up to levels of 50% dose reduction.

Biodegradable polysilsesquioxane nanoparticles as efficient contrast agents for magnetic resonance imaging.

Polysilsesquioxane (PSQ) nanoparticles are crosslinked homopolymers formed by condensation of functionalized trialkoxysilanes, and provide an interesting platform for developing biologically and biomedically relevant nanomaterials. In this work, the design and synthesis of biodegradable PSQ particles with extremely high payloads of paramagnetic Gd(III) centers is explored, for use as efficient contrast agents for magnetic resonance imaging (MRI). Two new bis(trialkoxysilyl) derivatives of Gd(III) diethylenetriamine pentaacetate (Gd-DTPA) containing disulfide linkages are synthesized and used to form biodegradable Gd-PSQ particles by base-catalyzed condensation reactions in reverse microemulsions. The Gd-PSQ particles, PSQ-1 and PSQ-2, carry 53.8 wt% and 49.3 wt% of Gd-DTPA derivatives, respectively. In addition, the surface carboxy groups on the PSQ-2 particles can be modified with polyethylene glycol (PEG) and the anisamide (AA) ligand to enhance biocompatibility and cell uptake, respectively. The Gd-PSQ particles are readily degradable to release the constituent Gd(III) chelates in the presence of endogenous reducing agents such as cysteine and glutathione. The MR relaxivities of the Gd-PSQ particles are determined using a 3T MR scanner, with r1 values ranging from 5.9 to 17.8 mMs(-1) on a per-Gd basis. Finally, the high sensitivity of the Gd-PSQ particles as T1 -weighted MR contrast agents is demonstrated with in vitro MR imaging of human lung and pancreatic cancer cells. The enhanced efficiency of the anisamide-functionalized PSQ-2 particles as a contrast agent is corroborated by both confocal laser scanning microscopy imaging and ICP-MS analysis of Gd content in vitro.

Improved performance of SPECT-CT In-111 capromab pendetide by correlation with diffusion-weighted magnetic resonance imaging for identifying metastatic pelvic lymphadenopathy in prostate cancer.

PURPOSE: To preliminarily evaluate the potential for an improvement in diagnostic performance by a combined interpretation of In-111 capromab pendetide single photon emission computed tomography (SPECT) including computed tomography (CT) image fusion with magnetic resonance diffusion-weighted imaging (MR-DWI) for identifying prostate cancer in pelvic lymph nodes thru correlation with histopathology. MATERIALS AND METHODS: This institutional approved, retrospective study identified patients with available histopathology of lymph nodes removed at the time of radical prostatectomy and who had undergone staging with In-111 capromab pendetide SPECT-CT and/or pelvic MRI (including DWI). The performance of In-111 capromab pendetide SPECT for identifying malignant lymph nodes was assessed. Subsequently, a combined reading of In-111 capromab pendetide SPECT and prostate MRI with DWI was performed and the performance assessed. RESULTS: 18 patients underwent In-111 capromab pendetide SPECT-CT. Of these, 12 patients had also undergone imaging with MR-DWI. In-111 capromab pendetide SPECT-CT had a sensitivity of 40.0% and specificity of 96.7% for identification of malignant lymph nodes. However, In-111 capromab pendetide SPECT-CT combined with MRI with DWI had a sensitivity of 88.9% and specificity of 98.5%. CONCLUSIONS: The addition of MR-DWI to the interpretation of In-111 capromab pendetide SPECT-CT may increase the sensitivity for detecting malignant lymph nodes in prostate cancer. Future prospective evaluation of combined In-111 capromab pendetide SPECT-CT and MR-DWI is indicated and may improve clinical evaluation of nodal disease in prostate cancer.

Diagnostic performance of In-111 capromab pendetide SPECT/CT in localized and metastatic prostate cancer.

PURPOSE: To determine the diagnostic performance of In-111 capromab pendetide single photon emission computed tomography/computed tomography (SPECT/CT), in the prostate gland, seminal vesicles, and lymph nodes via correlation to a gold standard of histopathology. MATERIALS AND METHODS: In this study, we retrospectively reviewed all In-111 capromab pendetide SPECT/CT acquired at our institution for dedicated histopathology within a 4-month period. Statistical measures of performance were calculated in terms of glandular, seminal vesicle, and lymph node activity. The accuracies of glandular and seminal vesicle activity were then correlated to the indices of risk, including the stage, Gleason score, and prostate-specific antigen level, as well as the treatment history. RESULTS: Of the 200 scans meeting the criteria of our study, 197 had prostate gland histopathology, 94 had bilateral seminal vesicle histopathology, and 5 had a total of 43 resected lymph nodes for comparison. The overall accuracies of the scan results were determined to be 77.7% (area under the receiver operating characteristic curve [AUC] = 0.539) for the gland, 67.0% (AUC = 0.510) for the seminal vesicles, and 93.0% (AUC = 0.787) for lymph nodes. For glandular activity alone, scan accuracy was found to significantly improve with increasing Gleason score (P < 0.0001), and in a setting prior to treatment (P = 0.0005). No statistically significant differences were found between different scan groups with regards to seminal vesicle activity. CONCLUSIONS: The results of this study provide substantiating evidence In-111 capromab pendetide can be used to accurately diagnose lymph node metastases from primary cancers of the prostate; however, they also suggest the test may have limited utility in diagnosing tumors within the prostate gland and seminal vesicles.

Modular synthesis of functional nanoscale coordination polymers.

The coordination-directed assembly of metal ions and organic bridging ligands has afforded a variety of bulk-scale hybrid materials with promising characteristics for a number of practical applications, such as gas storage and heterogeneous catalysis. Recently, so-called coordination polymers have emerged as a new class of hybrid nanomaterials. Herein, we highlight advances in the syntheses of both amorphous and crystalline nanoscale coordination polymers. We also illustrate how scaling down these materials to the nano-regime has enabled their use in a broad range of applications including catalysis, spin-crossover, templating, biosensing, biomedical imaging, and anticancer drug delivery. These results underscore the exciting opportunities of developing next-generation functional nanomaterials based on molecular components.

Manganese-based nanoscale metal-organic frameworks for magnetic resonance imaging.

Manganese-containing nanoscale metal-organic frameworks (NMOFs) with controllable morphologies were synthesized using reverse-phase microemulsion techniques at room temperature and a surfactant-assisted procedure at 120 degrees C with microwave heating. The nanoparticles were characterized using a variety of methods including SEM, TEM, TGA, PXRD, and ICP-MS. Although the nanoparticles gave a modest longitudinal relaxivity (r1) on a per Mn basis, they provided an efficient vehicle for the delivery of large doses of Mn2+ ions which exhibited very high in vitro and in vivo r1 values and afforded excellent MR contrast enhancement. The particle surface was also modified with a silica shell to allow covalent attachment of a cyclic RGD peptide and an organic fluorophore. The cell-targeting molecules on the Mn NMOFs enhanced their delivery to cancer cells to allow for target-specific MR imaging in vitro. The MR contrast enhancement was also demonstrated in vivo using a mouse model. Such core-shell hybrid nanostructures provide an ideal platform for targeted delivery of other imaging and therapeutic agents to diseased tissues.

Nanoscale coordination polymers for platinum-based anticancer drug delivery.

Pt-containing nanoscale coordination polymer (NCP) particles with the formula of Tb2(DSCP)3(H2O)12 (where DSCP represents disuccinatocisplatin), NCP-1, were precipitated from an aqueous solution of Tb3+ ions and DSCP bridging ligands via the addition of a poor solvent. SEM and TEM images showed that as-synthesized NCP-1 exhibited a spherical morphology with a DLS diameter of 58.3 +/- 11.3 nm. NCP-1 particles were stabilized against rapid dissolution in water by encapsulation in shells of amorphous silica. The resulting silica-coated particles NCP-1' exhibited significantly longer half-lives for DSCP release from the particles (a t1/2 of 9 h for NCP-1' with 7 nm silica coating vs t1/2 of 1 h for as-synthesized NCP-1). In vitro cancer cell cytotoxicity assays with the human colon carcinoma cell line (HT-29) showed that internalized NCP-1' particles readily released the DSCP moieties which were presumably reduced to cytotoxic Pt(II) species to give the Pt-containing NCPs anticancer efficacy superior to the cisplatin standard. The generality of this degradable nanoparticle formulation should allow for the design of NCPs as effective delivery vehicles for a variety of biologically and medically important cargoes such as therapeutic and imaging agents.