Complementary Imaging Methods Research Articles

Label-Free Interference Imaging of Intracellular Trafficking.

Intracellular cargo trafficking is a highly regulated process responsible for transporting vital cellular components to their designated destinations. This intricate journey has been a central focus of cellular biology for many years. Early investigations leaned heavily on biochemical and genetic approaches, offering valuable insight into molecular mechanisms of cellular trafficking. However, while informative, these methods lack the capacity to capture the dynamic nature of intracellular trafficking. The advent of fluorescent protein tagging techniques transformed our ability to monitor the complete lifecycle of intracellular cargos, advancing our understanding. Yet, a central question remains: How do these cargos manage to navigate through traffic challenges, such as congestion, within the crowded cellular environment? Fluorescence-based imaging, though valuable, has inherent limitations when it comes to addressing the aforementioned question. It is prone to photobleaching, making long-term live-cell imaging challenging. Furthermore, they render unlabeled cellular constituents invisible, thereby missing critical environmental information. Notably, the unlabeled majority likely exerts a significant influence on the observed behavior of labeled molecules. These considerations underscore the necessity of developing complementary label-free imaging methods to overcome the limitations of fluorescence imaging or to integrate them synergistically.In this Account, we outline how label-free interference-based imaging has the potential to revolutionize the study of intracellular traffic by offering unprecedented levels of detail. We begin with a brief introduction to our previous findings in live-cell research enabled by interferometric scattering (iSCAT) microscopy, showcasing its aptitude and adeptness in elucidating intricate nanoscale intracellular structures. As we delved deeper into our exploration, we succeeded in the label-free visualization of the entire lifespan of nanoscale protein complexes known as nascent adhesions (NAs) and the dynamic events associated with adhesions within living cells. Our continuous efforts have led to the development of Dynamic Scattering-particle Localization Interference Microscopy (DySLIM), a generalized concept of cargo-localization iSCAT (CL-iSCAT). This label-free, high-speed imaging method, armed with iSCAT detection sensitivity, empowers us to capture quantitative and biophysical insights into cargo transport, providing a realistic view of the intricate nanoscale logistics occurring within living cells. Our in vivo studies demonstrate that intracellular cargos regularly contend with substantial traffic within the crowded cellular environment. Simultaneously, they employ inherent strategies for efficient cargo transport, such as collective migration and hitchhiking, to enhance overall transport rates─intriguingly paralleling the principle and practice of urban traffic management. We also highlight the synergistic benefits of combining DySLIM with chemical-selective fluorescent methods. This Account concludes with a "Conclusions and Outlook" section, outlining promising directions for future research and developments, with a particular emphasis on the functional application of iSCAT live-cell imaging. We aim to inspire further investigation into the efficient transport strategies employed by cells to surmount transportation challenges, shedding light on their significance in cellular phenomena.

Visualization of carious lesions with polarized and depolarized light microscopy

Polarized light microscopy (PLM) is an established method in dental histology for investigating the ultrastructure and carious process of teeth. This study introduces a novel approach for measuring the degree of polarization (DOP) in a modified PLM setup and uses the DOP to assess the changes of the optical properties of enamel and dentin due to caries. The validation is provided by a comparison with complementary imaging methods, i.e. standard PLM and µCT. The results show that demineralization is reliably displayed by the DOP in accordance with the common imaging methods, and that this quantitative analysis of depolarization allows the characterization of the different pathohistological zones of caries.

Non-destructive analysis of Pb-acid battery positive plates, based on neutron tomography

Notwithstanding the in-depth understanding of lead-acid battery degradation processes developed in a time-honored field of science, there is still wide scope for knowledge-based technological advancements, in particular, targeting positive plate (PP) durability. Non-destructive imaging of the internal morphology, structure and chemistry of these components, enabled by neutron-based methods, is capable of disclosing otherwise inaccessible observables, that can form the factual basis for new pathways to device improvement. In this study, we propose a post mortem investigation of as-formed and electrochemically aged PPs, centered on neutron tomography and complemented by x-ray radiography and scanning-electron microscopy. These complementary imaging methods, thriving on different contrast mechanisms, allow 2D/3D position-sensitive morphological analyses of the nature and evolution of the positive active material (PAM) and of the spines of the PP, including: morphology variation, crack location, porosity distribution and identification of hydrogenated compounds. Specifically, in this work, we have pinpointed the differences in degradation modes—resulting from the application of a standard ageing protocol—of PPs fabricated in two technologically alternative ways: punching and gravity-casting, showing the superiority of the formed in terms of electrode stability upon charging abuse conditions.

An Inexpensive, Portable Shield to Improve Healthcare Worker Safety During Intubation Procedures.

Healthcare workers (HCW) are exposed to risk of infection during intubation procedures, in particular, in the prehospital setting. Here, we demonstrate a novel shield that can be used during intubation to block aerosols and droplets from reaching the HCW. The device is mounted on the patient's head and provides a barrier between patient and HCW. It incorporates a self-sealing port through which an endotracheal tube can be inserted. The port "floats" in the plane of the shield to facilitate maneuvering of the endotracheal tube. The shield is fabricated from transparent materials to enable the HCW to visualize the procedure. Using two complementary imaging methods, background oriented Schlieren imaging and laser sheet droplet imaging, we show that the device prevents detectable transmission of gas flow and droplets through the shield both before and after endotracheal tube insertion.Clinical Relevance- This device has the potential to protect HCWs from infections during intubation procedures, especially in the prehospital setting.

Diagnosis of Left-Sided Mechanical Prosthetic Valve Thrombosis: A Pictorial Review.

Although transcatheter valve therapy is rapidly evolving, surgical valve replacement is still required in many patients with severe left-side valve stenosis or regurgitation, the mechanical bi-leaflet heart valve being the standard prosthesis type in younger patients. Moreover, the prevalence of valvular heart disease is steadily increasing, especially in industrialized countries, and the problem of lifelong efficient anticoagulation of these patients remains fundamental, especially in the context where vitamin K antagonists continue to be the current standard of anticoagulation despite a level of oscillating anticoagulation. In this setting, avoiding prosthetic valve thrombosis after surgery is the number one objective for both the patient and the responsible physicians. Although rare, this complication is life threatening, with the sudden onset of acute cardiac failure such as acute pulmonary edema, cardiogenic shock, or sudden cardiac death and inadequate anticoagulation remaining the leading cause of prosthesis thrombosis, along with other risk factors. The availability of multimodal imaging techniques enables and encompasses to a full extent the diagnosis of mechanical valve thrombosis. The gold-standard diagnostic methods are transthoracic and transesophageal echocardiography. Moreover, 3D ultrasound has undoubted value in giving a more accurate description of the thrombus's extension. When transthoracic and transesophageal echocardiography are uncertain, the multidetector computer tomography examination is an important complementary imaging method. Fluoroscopy is also an excellent tool for evaluating the mobility of prosthetic discs. Each method complements the other to differentiate an acute mechanical valve thrombosis from other prosthetic valve pathologies such as pannus formation or infective endocarditis and aids the physician in accurately establishing the treatment method (surgical or pharmaceutical) and its optimal timing. The aim of this pictorial review was to discuss from an imagistic perspective the mechanical prosthetic aortic and mitral valve thrombosis and to provide an overview of the essential role of non-invasive exploration in the treatment of this severe complication.

A multimodal scanner coupling XRF, UV–Vis–NIR photoluminescence and Vis–NIR–SWIR reflectance imaging spectroscopy for cultural heritage studies

AbstractScanning x‐ray fluorescence (MA‐XRF), Reflectance Imaging Spectroscopy (RIS) and Luminescence Imaging Spectroscopy (LIS) are scientific methods extensively used in the investigation of artworks in Cultural Heritage Science. Nevertheless, these three highly complementary imaging methods have never been implemented in a single instrument. In this paper, we present a scanning system that is the first to simultaneously combine MA‐XRF, RIS, and LIS techniques, generating spatially aligned hyperspectral datasets. The specifications of the instrument and of the collected datacubes are described, together with the processing pipeline developed for the coupled exploitation and interpretation. The operation of this instrument, combining XRF with RIS and LIS mapping in an extended range (400–2500 nm and 200–1000 nm, respectively), is exemplified on an anonymous test painting, studied previously. A focus on a restored area of this painting allows to illustrates the complementarity of the three aforementioned methods, for the visualization and characterization of pigments, varnish, and binders.

Optical Coherence Tomography Angiography (OCT-A) in Uveitis: A Literature Review and a Reassessment of Its Real Role.

The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection. The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A. A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted. Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were "complementary to dye methods", "adjunct", "supplementing" and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified. To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research.

Retrospective motion correction in foetal MRI for clinical applications: existing methods, applications and integration into clinical practice.

Foetal MRI is a complementary imaging method to antenatal ultrasound. It provides advanced information for detection and characterisation of foetal brain and body anomalies. Even though modern single shot sequences allow fast acquisition of 2D slices with high in-plane image quality, foetal MRI is intrinsically corrupted by motion. Foetal motion leads to loss of structural continuity and corrupted 3D volumetric information in stacks of slices. Furthermore, the arbitrary and constantly changing position of the foetus requires dynamic readjustment of acquisition planes during scanning.

Characterization of cellular senescence in aging skeletal muscle.

Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses p16 Ink4a together with multiple senescence-related genes and, concomitantly, exhibits DNA damage and chromatin reorganization. Through analysis of isolated myofibers, we also detail a senescence phenotype within a subset of old cells, governed instead by p2 Cip1 . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.

White matter properties underlying reading abilities differ in 8-year-old children born full term and preterm: A multi-modal approach

Many diffusion magnetic resonance imaging (dMRI) studies document associations between reading skills and fractional anisotropy (FA) within brain white matter, suggesting that efficient transfer of information across the brain contributes to individual differences in reading. Use of complementary imaging methods can determine if these associations relate to myelin content of white matter tracts. Compared to children born at term (FT), children born preterm (PT) are at risk for reading deficits. We used two MRI methods to calculate associations of reading and white matter properties in FT and PT children. Participants (N=79: 36 FT and 43 PT) were administered the Gray's Oral Reading Test at age 8. We segmented three dorsal (left arcuate and bilateral superior longitudinal fasciculus) and four ventral (bilateral inferior longitudinal fasciculus and bilateral uncinate) tracts and quantified (1) FA from dMRI and (2) R1 from quantitative T1 relaxometry. We examined correlations between reading scores and these metrics along the trajectories of the tracts. Reading positively correlated with FA in segments of left arcuate and bilateral superior longitudinal fasciculi in FT children; no FA associations were found in PT children. Reading positively correlated with R1 in segments of the left superior longitudinal, right uncinate, and left inferior longitudinal fasciculi in PT children; no R1 associations were found in FT children. Birth group significantly moderated the associations of reading and white matter metrics. Myelin content of white matter may contribute to individual differences in PT but not FT children.

Cervical lymph node metastases in papillary thyroid cancer: Preoperative staging with ultrasound and/or computed tomography.

Preoperative screening of potential risk of lymph node metastasis is necessary for thyroidectomy plus lymph node dissection. The 2015 American thyroid association management guidelines do not recommend prophylactic cervical lymph node resection without clinical evidence of metastasis. Ultrasound is recommended imaging method and routine computed tomography is not recommended by the 2015 American thyroid association management guidelines for screening of lymph node metastasis. The objective of the study was to compare the diagnostic performance of ultrasound against that of computed tomography for screening cervical lymph node metastasis of patients with papillary thyroid cancer before thyroidectomy plus lymph node dissection.Data regarding preoperative neck ultrasound, neck computed tomography, and physical examination of the head and neck and postoperative pathological results of a total of 185 patients (age > 18 years) with a diagnosis of papillary thyroid cancer who had suspicious lymph nodes on preoperative imaging and treated by thyroidectomy plus lymph node dissection for the therapeutic purpose were collected and analyzed.Sensitivity (78.09% vs 75.28%, P < .0001) and accuracy (77.29% vs 75.13%, P = .0004) of neck computed tomography scanning to detect cervical lymph node metastasis were higher than those of neck ultrasound scanning. Sensitivity, accuracy, positive clinical utility, and negative clinical utility for neck ultrasound scanning plus neck computed tomography scanning to detect cervical lymph node metastasis were higher among all index tests (P < .05 for all) and were statistically the same as those of surgical pathology (P > .05 for all). The working areas for decision-making of thyroidectomy plus lymph node dissection of the physical examination, neck ultrasound, the neck computed tomography, and the neck ultrasound scanning plus the neck computed tomography scanning were 0 to 0.691 diagnostic confidence/lesion, 0 to 0.961 diagnostic confidence/lesion, 0 to 0.944 diagnostic confidence/lesion, and 0 to 0.981 diagnostic confidence/lesion, respectively.Besides the neck ultrasound, the neck computed tomography scanning can be used as a complementary imaging method to detect cervical lymph node metastasis of patients with papillary thyroid cancer before thyroidectomy plus lymph node dissection.Level of evidence: III.Technical efficacy stage: 2.

Comparison of [68Ga]-FAPI PET/CT and [18F]-FDG PET/CT in Multiple Myeloma: Clinical Experience.

Objective: In this study, we aimed to compare [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging to detect lesions in multiple myeloma. Methods: A total of 14 patients with multiple myeloma who underwent [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging were included in this retrospective study. SUVmax values of [68Ga]FAPI and [18F]FDG were compared according to lesion locations. Also, lesion localization ability of both imaging methods was compared on the patient basis. Results: In 4 of 14 patients, [68Ga]FAPI PET/CT and [18F]FDG PET/CT have not detected any bone lesions. In 8 of the remaining 10 patients [18F]FDG PET/CT detected bone lesions but in this group, 6 patients showed more higher SUVmax values than [18F]FDG PET/CT in [68Ga]FAPI PET/CT.In contrast, 2 of 8 patients showed more higher SUVmax values than [68Ga]FAPI PET/CT in [18F]FDG PET/CT. Moreover, [68Ga]FAPI PET/CT detected bone lesions in two patients, which werenot detected by [18F]FDG PET/CT. Also, in five patients, [68Ga]FAPI PET/CT showed more bone lesions in comparison with[18F]FDG PET/CT. Only one patient, [18F]FDG PET/CT showed more bone lesions. Three extramedullary involvements were observed in the following locations: lung, presacral lymph node, and soft tissue mass lateral to the right maxillary sinus. Among these involvements, higher SUVmax values were observed in the lung and presacral lymph node with [68Ga]FAPI compared to [18F]FDG. However, the soft tissue mass showed a higher SUVmax value in [18F]FDG than [68Ga]FAPI. Conclusions: No significant superiority was observed in [68Ga]FAPI PET/CT over [18F]FDG PET/CT in patients with MM. However, [68Ga]FAPI PET/CT can be utilized as a complementary imaging method to [18F]FDG PET/CT in some settings, especially in low-[18F]FDG affinity and inconclusive cases. Considering the favorable aspects of [68Ga]FAPI PET/CT in MM, such as low background activity, absence of non-specific bone marrow, and physiological brain involvement, further studies with a larger sample size should be conducted.

New insights into René Magritte's early surrealist painting La salle d'armes

Painted in 1925 or 1926, over an older composition, La salle d'armes, is among the first Magritte's surrealist paintings. It is also one of the only four Magritte's using enamels reported in the René Magritte Catalog Raisonné. This paper presents the material and technical study conducted on this double painting. The complementary imaging and analytical methods applied for this purpose provided substantial information on both, the visible image and the hidden one. Concerning the latter, for instance, the obtained results permitted to identify a cubo‐futurist oil painting from the very early 1920s.

Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study

Emerging data indicate that genomic alterations can shape immune cell composition in early breast cancer. However, there is a need for complementary imaging and sequencing methods for the quantitative assessment of combined somatic copy number alteration (SCNA) and immune profiling in pathological samples. Here, we tested the feasibility of three approaches—CUTseq, for high-throughput low-input SCNA profiling, multiplexed fluorescent immunohistochemistry (mfIHC) and digital-image analysis (DIA) for quantitative immuno-profiling- in archival formalin-fixed paraffin-embedded (FFPE) tissue samples from patients enrolled in the randomized SBG-2004-1 phase II trial. CUTseq was able to reproducibly identify amplification and deletion events with a resolution of 100 kb using only 6 ng of DNA extracted from FFPE tissue and pooling together 77 samples into the same sequencing library. In the same samples, mfIHC revealed that CD4 + T-cells and CD68 + macrophages were the most abundant immune cells and they mostly expressed PD-L1 and PD-1. Combined analysis showed that the SCNA burden was inversely associated with lymphocytic infiltration. Our results set the basis for further applications of CUTseq, mfIHC and DIA to larger cohorts of early breast cancer patients.

Synthesis of ultrathin rhenium disulfide nanoribbons using nano test tubes

The synthesis of ultrathin rhenium disulfide (ReS2) nanoribbons within single-walled carbon nanotubes (SWNTs) has been established. Dirhenium decacarbonyl complex is encapsulated into the SWNTs to provide a source of confined rhenium atoms, which readily react with iodine to form discrete nm-sized clusters of rhenium iodide [Re6I14]2− embedded in the nanotubes. The final step of the synthesis is accomplished by admitting hydrogen sulfide gas into nano test tubes, yielding twisted nanoribbons of rhenium disulfide encapsulated in carbon nanotubes, ReS2@SWNTs. The width, structure, and composition of rhenium disulfide nanoribbons are strictly controlled by the extreme confinement of the host-SWNT. A holistic analytical approach combining complementary imaging and analysis methods is used at each synthetic step to elucidate the structure and composition of the guest material and reveal the role of the SWNT contributing towards the electronic interactions with encapsulated inorganic structures. As ReS2 nanoribbons are expected to retain the electronic properties of the bulk material, such as direct bandgap, the low dimensional form of this material can be of interest for use in nanoscale electronic devices.

Complementary Imaging Method: Applicability of Raster-stereography and Validation by Radiography

Complementary Imaging Method: Applicability of Raster-stereography and Validation by Radiography

Simulation of an imaging system for internal contamination of lungs using MPA-MURA coded-aperture collimator

The nuclides inhaled during nuclear accidents usually cause internal contamination of the lungs with low activity. Although a parallel-hole imaging system, which is widely used in medical gamma cameras, has a high resolution and good image quality, owing to its extremely low detection efficiency, it remains difficult to obtain images of inhaled lung contamination. In this study, the Monte Carlo method was used to study the internal lung contamination imaging using the MPA-MURA coded-aperture collimator. The imaging system consisted of an adult male lung model, with a mosaicked, pattern-centered, and anti-symmetric MURA coded-aperture collimator model and a CsI (Tl) detector model. The MLEM decoding algorithm was used to reconstruct the internal contamination image, and the complementary imaging method was used to reduce the number of artifacts. The full width at half maximum of the I-131 point source image reconstructed by the MPA-MURA coded-aperture imaging reached 2.51 mm, and the signal-to-noise ratio of the simplified respiratory tract source (I-131) image reconstructed through MPA-MURA coded-aperture imaging was 3.98 dB. Although the spatial resolution of MPA-MURA coded-aperture imaging is not as good as that of parallel-hole imaging, the detection efficiency of PMA-MURA coded-aperture imaging is two orders of magnitude higher than that of parallel-hole collimator imaging. Considering the low activity level of internal lung contamination caused by nuclear accidents, PMA-MURA coded-aperture imaging has significant potential for the development of lung contamination imaging.

Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment.

Although lower grade gliomas are driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene and are less aggressive than primary glioblastoma, they nonetheless generally recur. IDH1-mutant patients are increasingly being treated with temozolomide, but early detection of response remains a challenge and there is a need for complementary imaging methods to assess response to therapy prior to tumor shrinkage. The goal of this study was to determine the value of magnetic resonance spectroscopy (MRS)-based metabolic changes for detection of response to temozolomide in both genetically engineered and patient-derived mutant IDH1 models. Using 1H MRS in combination with chemometrics identified several metabolic alterations in temozolomide-treated cells, including a significant increase in steady-state glutamate levels. This was confirmed in vivo, where the observed 1H MRS increase in glutamate/glutamine occurred prior to tumor shrinkage. Cells labeled with [1-13C]glucose and [3-13C]glutamine, the principal sources of cellular glutamate, showed that flux to glutamate both from glucose via the tricarboxylic acid cycle and from glutamine were increased following temozolomide treatment. In line with these results, hyperpolarized [5-13C]glutamate produced from [2-13C]pyruvate and hyperpolarized [1-13C]glutamate produced from [1-13C]α-ketoglutarate were significantly higher in temozolomide-treated cells compared with controls. Collectively, our findings identify 1H MRS-detectable elevation of glutamate and hyperpolarized 13C MRS-detectable glutamate production from either pyruvate or α-ketoglutarate as potential translatable metabolic biomarkers of response to temozolomide treatment in mutant IDH1 glioma. SIGNIFICANCE: These findings show that glutamate can be used as a noninvasive, imageable metabolic marker for early assessment of tumor response to temozolomide, with the potential to improve treatment strategies for mutant IDH1 patients.

Survey on Van Gogh\u2019s early painting technique through the non-invasive and multi analytical study of Head of peasant

The strong lighting of the face against a dark background, the bold brushstroke and the model’s expressiveness that characterize Van Gogh’s Head of peasant, belonging to the Royal Museums of Fine Arts of Belgium collections, are typical features found in the peasant heads studies painted in Nuenen, in March–April 1885, in prevision of the well-known The Potato Eaters. However, this oil painting additionally testifies of Van Gogh’s early experiments in regards with the laws of colors, the flesh rendering and portraying models under artificial light. In order to collect material and technical information revealing how the painter practically handled these issues, the Brussels peasant head has been investigated in situ by complementary non-invasive imaging and analytical methods. While the identified pigments strictly reflect Van Gogh’s palette in Nuenen, relevant outcomes regarding the flesh tones composition, the rendered forceful expression of the figure, the effect of a face painted by lamplight, and the use of simultaneous color contrasts were achieved.

An Imaging Toolkit for Physical Characterization of Long-Acting Pharmaceutical Implants

In pharmaceutical development alternative drug delivery modalities are being increasingly employed. One example is an implant, which achieves gradual drug release in patients over a period of many months or years. Due to the complexity of these long-acting formulations, advanced physical characterization methods are desirable as screening tools during protracted formulation development. Imaging methods are of particular interest due to their ability to interrogate the structure and composition of implants spatially across multiple length scales (macro, micro, nano). In this work, spatiochemical imaging is shown to interrogate many crucial drug product attributes of solid implants: overall implant structure, drug distribution, micro-domain size and orientation, agglomeration, porosity and defects, drug/excipient interface, dissolution process, and release mechanism. Imaging methods facilitate a detailed understanding of the process/structure correlation to inform on formulation selection, process parameter optimization, and batch consistency. Numerous case studies of implant applications with imaging are discussed. Methods utilized are X-ray computed tomography (XRCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) imaging, and Raman microscopy. The imaging data is complemented with solid-state nuclear magnetic resonance (ssNMR). Altogether, these examples demonstrate that complementary imaging methods are highly effective for analyzing complex and novel pharmaceutical modalities such as solid implants.