high-resolution-cardiac-positron-emission-tomographycomputed

High-Resolution Cardiac Positron Emission Tomography/Computed Tomography for Small Animals

Positron emission tomography (PET) and computed tomography (CT) are among the most employed diagnostic imaging techniques, and both serve in understanding ...

CNR Institute of Clinical Physiology

The integration of complementary information from different medical imaging techniques opened, since the 90s, new scenarios and possibilities for non-invasive diagnosis. The anatomo-functional information obtained with the image fusion (i.e., by composing PET and CT or SPECT and CT), is greater than the sum of information given by each modality, and allows quantitative evaluation of functional parameters through the application of specific model-based image processing. Before the introduction of integrated multimodal scanners from most manufacturers (hardware fusion), many software techniques have been used to allow image fusion from different modalities; such methods of software fusion is still important for all modalities that cannot by merged in a single scanner, or whenever the patient movement can introduce inter-modality misalignments within the same exam in an integrated scanner or if each modality is utilized at different times and on separate scanners. This article summarizes the software and hardware evolution of clinical and preclinical hybrid imaging, and discusses the outcome of this technology in the clinical environment with particular emphasis on the cardiovascular application.

[Hybrid imaging: present and future of non-invasive diagnosis].

The αvβ3 integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel (68)Ga-2,2',2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI.

MicroPET/CT imaging of αvβ₃ integrin via a novel ⁶⁸Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction.

Micro-CT is an established imaging technique for high-resolution non-destructive assessment of vascular samples, which is gaining growing interest for investigations of atherosclerotic arteries both in humans and in animal models. However, there is still a lack in the definition of micro-CT image metrics suitable for comprehensive evaluation and quantification of features of interest in the field of experimental atherosclerosis (ATS).

Quantitative micro-CT based coronary artery profiling using interactive local thresholding and cylindrical coordinates.

In this contribution, we present a morphological description and comparative morphometric analysis of Cavallo D, a human tooth unearthed from the Mousterian FIII sublayer of Grotta del Cavallo (Apulia, Italy).

Middle paleolithic human deciduous incisor from Grotta del Cavallo, Italy.

Laser-driven electron accelerators are capable of producing high-energy electron bunches in shorter distances than conventional radiofrequency accelerators. To date, our knowledge of the radiobiological effects in cells exposed to electrons using a laser-plasma accelerator is still very limited. In this study, we compared the dose-response curves for micronucleus (MN) frequency and telomere length in peripheral blood lymphocytes exposed to laser-driven electron pulse and X-ray radiations. Additionally, we evaluated the effects on cell survival of in vitro tumor cells after exposure to laser-driven electron pulse compared to electron beams produced by a conventional radiofrequency accelerator used for intraoperative radiation therapy. Blood samples from two different donors were exposed to six radiation doses ranging from 0 to 2 Gy. Relative biological effectiveness (RBE) for micronucleus induction was calculated from the alpha coefficients for electrons compared to X rays (RBE = alpha laser/alpha X rays). Cell viability was monitored in the OVCAR-3 ovarian cancer cell line using trypan blue exclusion assay at day 3, 5 and 7 postirradiation (2, 4, 6, 8 and 10 Gy). The RBE values obtained by comparing the alpha values were 1.3 and 1.2 for the two donors. Mean telomere length was also found to be reduced in a significant dose-dependent manner after irradiation with both electrons and X rays in both donors studied. Our findings showed a radiobiological response as mirrored by the induction of micronuclei and shortening of telomere as well as by the reduction of cell survival in blood samples and cancer cells exposed in vitro to laser-generated electron bunches. Additional studies are needed to improve preclinical validation of the radiobiological characteristics and efficacy of laser-driven electron accelerators in the future.

Radiobiological Effectiveness of Ultrashort Laser-Driven Electron Bunches: Micronucleus Frequency, Telomere Shortening and Cell Viability.

The aim of the study is the assessment of Nadale 1, a Neanderthal deciduous tooth recently discovered in Northeastern Italy in the De Nadale cave (Middle Palaeolithic). Together with the clear archaeological context of the site, this study brings new insight on Neanderthal behavior and dental morphological variability.

A Neanderthal deciduous human molar with incipient carious infection from the Middle Palaeolithic De Nadale cave, Italy.

Enamel thickness figures prominently in studies of human evolution, particularly for taxonomy, phylogeny, and paleodietary reconstruction. Attention has focused on molar teeth, through the use of advanced imaging technologies and novel protocols. Despite the important results achieved thus far, further work is needed to investigate all tooth classes. We apply a recent approach developed for anterior teeth to investigate the 3D enamel thickness of Neandertal and modern human (MH) canines. In terms of crown size, the values obtained for both upper and lower unworn/slightly worn canines are significantly greater in Neandertals than in Upper Paleolithic and recent MH. The 3D relative enamel thickness (RET) is significantly lower in Neandertals than in MH. Moreover, differences in 3D RET values between the two groups appear to decrease in worn canines beginning from wear stage 3, suggesting that both the pattern and the stage of wear may have important effects on the 3D RET value. Nevertheless, the 3D average enamel thickness (AET) does not differ between the two groups. In both groups, 3D AET and 3D RET indices are greater in upper canines than in lower canines, and overall the enamel is thicker on the occlusal half of the labial aspect of the crown, particularly in MH. By contrast, the few early modern humans investigated show the highest volumes of enamel while for all other components of 3D enamel, thickness this group holds an intermediate position between Neandertals and recent MH. Overall, our study supports the general findings that Neandertals have relatively thinner enamel than MH (as also observed in molars), indicating that unworn/slightly worn canines can be successfully used to discriminate between the two groups. Further studies, however, are needed to understand whether these differences are functionally related or are the result of pleiotropic or genetic drift effects.

3D enamel thickness in Neandertal and modern human permanent canines.

The Uluzzian techno-complex is commonly considered to be a "transitional industry" mostly on the basis of some inferred characteristics such as a chiefly flake-based production, a small amount of Upper Palaeolithic-like tools and a combination of Middle and Upper Palaeolithic elements both in the toolkit and in the technical systems. Following its discovery, the Uluzzian was identified as the Italian counterpart of the French Châtelperronian and attributed to Neandertals. However, a study issued in 2011 has established the modern character of the two deciduous teeth found in 1964 in the Uluzzian deposit of Grotta del Cavallo, fostering renewed interests to the Uluzzian culture, which real nature is almost unknown to the international scientific community. Here we provide preliminary results of the study on the lithic assemblage from the earliest Uluzzian layer and on backed pieces from the whole Uluzzian sequence of Grotta del Cavallo (Apulia, Italy), the type site of the Uluzzian. Moreover, besides a thorough review on the stratigraphy of Grotta del Cavallo (Supplementary Materials), we provide updated information on the human remains by presenting two unpublished teeth from the reworked deposit of the same cave. We conclude that the early Uluzzians demonstrate original technological behavior and innovations devoid of any features deriving or directly linked with the late Mousterian of Southern Italy. Therefore, the novelty nature of the Uluzzian techno-complex (with respect to the preceding Mousterian) complies with the recent reassessment of the two deciduous teeth from Grotta del Cavallo in suggesting an earliest migration of modern humans in southern Europe around 45,000 years ago.

Grotta del Cavallo (Apulia-Southern Italy). The Uluzzian in the mirror.

Accurate dynamic three-dimensional (4D) imaging of the heart of small rodents is required for the preclinical study of cardiac biomechanics and their modification under pathological conditions, but technological challenges are met in laboratory practice due to the very small size and high pulse rate of the heart of mice and rats as compared to humans. In 4D X-ray microtomography (4D μCT), the achievable spatio-temporal resolution is hampered by limitations in conventional X-ray sources and detectors. Here, we propose a proof-of-principle 4D μCT platform, exploiting the unique spatial and temporal features of novel concept, all-optical X-ray sources based on Thomson scattering (TS). The main spatial and spectral properties of the photon source are investigated using a TS simulation code. The entire data acquisition workflow has been also simulated, using a novel 4D numerical phantom of a mouse chest with realistic intra- and inter-cycle motion. The image quality of a typical single 3D time frame has been studied using Monte Carlo simulations, taking into account the effects of the typical structure of the TS X-ray beam. Finally, we discuss the perspectives and shortcomings of the proposed platform.

Numerical simulation of novel concept 4D cardiac microtomography for small rodents based on all-optical Thomson scattering X-ray sources.

Computed Tomography (CT) has long been regarded as a purely anatomical imaging modality. Recent advances on CT technology and Contrast Agents (CA) in both clinical and preclinical cardiac imaging offer opportunities for the use of CT in functional imaging. Combined with modern ECG-gating techniques, functional CT has now become a reality allowing a comprehensive evaluation of myocardial global and regional function, perfusion and coronary angiography. This article aims at reviewing the current status of cardiac CT perfusion and micro-CT perfusion with established and experimental scanners and contrast agents, from clinical practice to the experimental domain of investigations based on animal models of heart diseases.

Cardiac Computed Tomography Perfusion: Contrast Agents, Challenges and Emerging Methodologies from Preclinical Research to the Clinics.

The site of Riparo Broion (Vicenza, northeastern Italy) preserves a stratigraphic sequence documenting the Middle-to-Upper Paleolithic transition, in particular the final Mousterian and the Uluzzian cultures. In 2018, a human tooth was retrieved from a late Mousterian level, representing the first human remain ever found from this rock shelter (Riparo Broion 1). Here, we provide the morphological description and taxonomic assessment of Riparo Broion 1 with the support of classic and virtual morphology, 2D and 3D analysis of the topography of enamel thickness, and DNA analysis. The tooth is an exfoliated right upper deciduous canine, and its general morphology and enamel thickness distribution support attribution to a Neanderthal child. Correspondingly, the mitochondrial DNA sequence from Riparo Broion 1 falls within the known genetic variation of Late Pleistocene Neanderthals, in accordance with newly obtained radiocarbon dates that point to approximately 48 ka cal BP as the most likely minimum age for this specimen. The present work describes novel and direct evidence of the late Neanderthal occupation in northern Italy that preceded the marked cultural and technological shift documented by the Uluzzian layers in the archaeological sequence at Riparo Broion. Here, we provide a new full morphological, morphometric, and taxonomic analysis of Riparo Broion 1, in addition to generating the wider reference sample of Neanderthal and modern human upper deciduous canines. This research contributes to increasing the sample of fossil remains from Italy, as well as the number of currently available upper deciduous canines, which are presently poorly documented in the scientific literature.

A late Neanderthal tooth from northeastern Italy.

To investigate microstructural alterations of explanted long-term central venous catheters of totally implantable venous access devices, using micro-computed tomography.

Comparative structural analysis of polyurethane and silicone catheters of totally implantable venous access devices by micro-computed tomography.

Flash radiotherapy (FLASH-RT) is currently being regarded as the next breakthrough in radiation treatment of cancer, delivering ultrahigh radiation doses in a very short time, and sparing normal tissues from detrimental injury. Here we review the current evidence on the preclinical findings as well as the radiobiological mechanisms underlying the FLASH effect. We also briefly examine the scenario of available technologies for delivering FLASH dose-rates for research and their implications for future clinical use.

FLASH ultra-high dose rates in radiotherapy: preclinical and radiobiological evidence.

The healing process of the tooth extraction socket often leads to significant resorption of the alveolar bone, eventually causing clinical difficulties for future implant-supported rehabilitations. The aim of the present animal study was to evaluate alveolar bone remodeling after tooth extraction in a rabbit model, either with or without the use of a plain collagen plug inside the socket, by means of micro-computed tomography. The study included the micro-tomography analysis of 36 rabbits' incisor extraction sockets, either left empty or filled with a collagen plug. All animals were euthanized in a staggered manner, in order to address molecular, histologic, and radiographic analyses at different time-points, up to 90 days after surgery. The three-dimensional evaluation was carried out using micro-computed tomography technology on excised bone blocks including the alveolus and the contralateral bone. Both linear and volumetric measures were recorded: the percentage of bone volume change (ΔBV) within the region of interest was considered the primary endpoint of the study. The micro-CT analysis revealed mean volumetric changes of -58.1% ± from baseline to 3 months for the control group, and almost no bone loss for the test group, -4.6%. The sockets treated with the collagen plug showed significantly less dimensional resorption, while the natural-healing group showed an evident collapse of the alveolar bone three months after extraction surgery.

Article	Year
[Hybrid imaging: present and future of non-invasive diagnosis]. Recenti progressi in medicina\| PubMed ID: 22677944	2012
MicroPET/CT imaging of αvβ₃ integrin via a novel ⁶⁸Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction. European journal of nuclear medicine and molecular imaging\| PubMed ID: 23674206	2013
Quantitative micro-CT based coronary artery profiling using interactive local thresholding and cylindrical coordinates. Technology and health care : official journal of the European Society for Engineering and Medicine\| PubMed ID: 26410117	2015
Middle paleolithic human deciduous incisor from Grotta del Cavallo, Italy. American journal of physical anthropology\| PubMed ID: 27365292	2016
Radiobiological Effectiveness of Ultrashort Laser-Driven Electron Bunches: Micronucleus Frequency, Telomere Shortening and Cell Viability. Radiation research\| PubMed ID: 27439449	2016
A Neanderthal deciduous human molar with incipient carious infection from the Middle Palaeolithic De Nadale cave, Italy. American journal of physical anthropology\| PubMed ID: 27704536	2017
3D enamel thickness in Neandertal and modern human permanent canines. Journal of human evolution\| PubMed ID: 29054166	2017
Grotta del Cavallo (Apulia-Southern Italy). The Uluzzian in the mirror. Journal of anthropological sciences = Rivista di antropologia : JASS\| PubMed ID: 30036183	2018
Numerical simulation of novel concept 4D cardiac microtomography for small rodents based on all-optical Thomson scattering X-ray sources. Scientific reports\| PubMed ID: 31186451	2019
Cardiac Computed Tomography Perfusion: Contrast Agents, Challenges and Emerging Methodologies from Preclinical Research to the Clinics. Academic radiology\| PubMed ID: 32220550	2021
A late Neanderthal tooth from northeastern Italy. Journal of human evolution\| PubMed ID: 32889336	2020
Comparative structural analysis of polyurethane and silicone catheters of totally implantable venous access devices by micro-computed tomography. SAGE open medicine\| PubMed ID: 34881041	2021
FLASH ultra-high dose rates in radiotherapy: preclinical and radiobiological evidence. International journal of radiation biology\| PubMed ID: 34913413	2022
Alveolar Bone Remodeling with or without Collagen Filling of the Extraction Socket: A High-Resolution X-ray Tomography Animal Study. Journal of clinical medicine\| PubMed ID: 35566619	2022

Daniele Panetta

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