Focal Spot, Summer 1991

https://digitalcommons.wustl.edu/focal_spot_archives/1058/thumbnail.jp

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

Medical Radiology: Current Progress

Recently, medical radiology has undergone significant improvements in patient management due to advancements in image acquisition by the last generation of machines, data processing, and the integration of artificial intelligence. In this way, cardiovascular imaging is one of the fastest-growing radiological subspecialties. In this study, a compressive review was focused on addressing how and why CT and MR have gained a I class indication in most cardiovascular diseases, and the potential impact of tissue and functional characterization by CT photon counting, quantitative MR mapping, and 4-D flow. Regarding rectal imaging, advances in cancer imaging using diffusion-weighted MRI sequences for identifying residual disease after neoadjuvant chemoradiotherapy and [18F] FDG PET/MRI were provided for high-resolution anatomical and functional data in oncological patients. The results present a large overview of the approach to the imaging of diffuse and focal liver diseases by US elastography, contrast-enhanced US, quantitative MRI, and CT for patient risk stratification. Italy is currently riding the wave of these improvements. The development of large networks will be crucial to create high-quality databases for patient-centered precision medicine using artificial intelligence. Dedicated radiologists with specific training and a close relationship with the referring clinicians will be essential human factors

MRI sequences for detection of acute pulmonary embolism

In recent years a range of imaging techniques have emerged to help diagnose patients with suspected acute Pulmonary Embolism (PE). This is particularly useful for those who are contraindicated (renal failure or allergies) to the contrast media that is needed to perform Computed Tomography Pulmonary Angiography (CTPA), which would be the usual diagnostic tool of choice. To aid the cohort of patients with this contraindication, we have investigated the option of using Magnetic Resonance Imaging (MRI) to diagnose PE. In this thesis, MRI sequences including gradient recall echo (more specifically balanced Steady State Free Precession [b-SSFP]) with different trajectories of data sampling, and diffusion weighted imaging (DWI) were assessed. None of the sequences investigated required the use of intravenous contrast media. In Study I, we investigated a group of positive PE patients (verified by CTPA) alongside a volunteer group, who provided a negative PE control cohort. A b-SSFP sequence was assessed, using repetitive sampling of each slice position, in three different orthogonal planes. No triggering or breath hold techniques were used during imaging. This technique produced a large number of slices at each location for evaluation by radiologist. An excellent specificity and a good sensitivity were achieved. In Study II, a group of positive PE patients (also verified by CTPA) and a control volunteer group were used to test the DWI technique, which is not used commonly for the investigation of thrombosis in the lungs. We compared DWI against the single slice per position approach of b-SSFP and CTPA, and demonstrated its capability to depict pulmonary embolism, finding a very high sensitivity but poor specificity for DWI. In Study III, we tested two different sampling techniques for b-SSFP, Cartesian standard and golden angle radial sampling trajectories, to image the pulmonary arteries in ten volunteers and in two patients who had PE. We demonstrated the improvement of image quality when using radial trajectory sampling in comparison to the Cartesian technique. We also demonstrated that the post-reconstruction ‘sliding window’ method could be applied to the golden angle radial sampling schema when a different temporal resolution is needed. In Study IV, we used the sequence tested in Study III (b-SSFP with golden angle radial and Cartesian sampling) in a clinical setting. The study included 64 patients who were suspected of having acute PE; all were examined while waiting for CTPA diagnostic testing. We compared radial sampling versus Cartesian, and also assessed post-reconstruction images of the radial sampling, with varying temporal resolution. The radial sampling with golden angle schema did not produce images of high enough quality to depict acute PE in patients. In study V, a retrospective overview of 57 patients (2012–2018) from our institution, with suspected acute PE was made. This group of patients was contraindicated to CTPA, and so were examined only using b-SSFP images. The clinical outcome of this cohort was obtained from the electronical medical record system up to twelve months after their MRI assessments. The MRI results allowed the clinicians to change or support their decision as to which treatment strategy they chose, in patients with or without PE

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

nuclear medicine; diagnostic radiolog

Non-Invasive Imaging for the Assessment of Cardiac Dose and Function Following Focused External Beam Irradiation

Technological advances in imaging and radiotherapy have led to significant improvement in the survival rate of breast cancer patients. However, a larger proportion of patients are now exhibiting the less understood, latent effects of incidental cardiac irradiation that occurs during left-sided breast radiotherapy. Here, we examine the utility of four-dimensional computed tomography (4D-CT) for the accurate assessment of cardiac dose; and a hybrid positron emission tomography (PET) magnetic resonance imaging (MRI) system to longitudinally study radiation-induced cardiac effects in a canine model. Using 4D-CT and deformable dose accumulation, we assessed the variation caused by breathing motion in the estimated dose to the heart, left-ventricle, and left anterior descending artery (LAD) of left-sided breast cancer patients. The LAD showed substantial variation in dose due to breathing. In light of this, we suggest the use of 4D-CT and dose accumulation for future clinical studies looking at the relationship between LAD dose and cardiac toxicity. Although symptoms of cardiac dysfunction may not manifest clinically for 10-15 years post radiation, PET-MRI can potentially identify earlier changes in cardiac inflammation and perfusion that are typically asymptomatic. Using PET-MRI, the progression of radiation-induced cardiac toxicity was assessed in a large animal model. Five canines were imaged using 13N-ammonia and 18F-fluorodeoxyglucose (FDG) PET-MRI to assess changes in myocardial perfusion and inflammation, respectively. All subjects were imaged at baseline, 1 week, 4 weeks, 3 months, 6 months, and 12 months after focused cardiac irradiation. To the best of our knowledge PET has not been previously used to assess cardiac perfusion following irradiation. The delivered dose to the heart, left ventricle, LAD, and left circumflex artery were comparable to what has been observed during breast radiotherapy. Relative to baseline, a transient increase in myocardial perfusion was observed followed by a gradual return to baseline. However, a persistent increase in FDG uptake was observed throughout the entire left ventricle, including both irradiated and less-irradiated portions of the heart. In light of these findings, we suggest the use of this imaging approach for future human studies to assess mitigation strategies aimed at minimizing cardiac exposure and long-term toxicity subsequent to left-sided breast irradiation

DICOM for EIT

With EIT starting to be used in routine clinical practice [1], it important that the clinically relevant information is portable between hospital data management systems. DICOM formats are widely used clinically and cover many imaging modalities, though not specifically EIT. We describe how existing DICOM specifications, can be repurposed as an interim solution, and basis from which a consensus EIT DICOM ‘Supplement’ (an extension to the standard) can be writte

Estimation of thorax shape for forward modelling in lungs EIT

The thorax models for pre-term babies are developed based on the CT scans from new-borns and their effect on image reconstruction is evaluated in comparison with other available models