This paper presents a review of automated image registration methodologies that have been used in the medical field. The aim of this paper is to be an introduction to the field, provide knowledge on the work that has been developed and to be a suitable reference for those who are looking for registration methods for a specific application. The registration methodologies under review are classified into intensity or feature based. The main steps of these methodologies, the common geometric transformations, the similarity measures and accuracy assessment techniques are introduced and described.

Currently, Nuclear Medicine has a clearly defined role in clinical practice due to its usefulness in many medical disciplines. It provides relevant diagnostic and therapeutic options leading to patients' healthcare and quality of life improvement. During the first two decades of the 21stt century, the number of Nuclear Medicine procedures increased considerably. Clinical and research advances in Nuclear Medicine and Molecular Imaging have been based on developments in radiopharmaceuticals and equipment, namely, the introduction of multimodality imaging. In addition, new therapeutic applications of radiopharmaceuticals, mainly in oncology, are underway. This review will focus on radiopharmaceuticals for positron emission tomography (PET), in particular, those labeled with Fluorine-18 and Gallium-68. Multimodality as a key player in clinical practice led to the development of new detector technology and combined efforts to improve resolution. The concept of dual probe (a single molecule labeled with a radionuclide for single photon emission computed tomography)/positron emission tomography and a light emitter for optical imaging) is gaining increasing acceptance, especially in minimally invasive radioguided surgery. The expansion of theranostics, using the same molecule for diagnosis (γ or positron emitter) and therapy (β minus or α emitter) is reshaping personalized medicine. Upcoming research and development efforts will lead to an even wider array of indications for Nuclear Medicine both in diagnosis and treatment.

The understanding of the natural history of Alzheimer’s disease (AD) and temporal trajectories of in vivo molecular mechanisms requires longitudinal approaches. A behavioral and multimodal imaging study was performed at 4/8/12 and 16 months of age in a triple transgenic mouse model of AD (3xTg-AD). Behavioral assessment included the open field and novel object recognition tests. Molecular characterization evaluated hippocampal levels of amyloid β (Aβ) and hyperphosphorylated tau. Magnetic resonance imaging (MRI) included assessment of hippocampal structural integrity, blood–brain barrier (BBB) permeability and neurospectroscopy to determine levels of the endogenous neuroprotector taurine. Longitudinal brain amyloid accumulation was assessed using ¹¹C Pittsburgh compound B positron emission tomography (PET), and neuroinflammation/microglia activation was investigated using ¹¹C-PK1195. We found altered locomotor activity at months 4/8 and 16 months and recognition memory impairment at all time points. Substantial early reduction of hippocampal volume started at month 4 and progressed over 8/12 and 16 months. Hippocampal taurine levels were significantly decreased in the hippocampus at months 4/8 and 16. No differences were found for amyloid and neuroinflammation with PET, and BBB was disrupted only at month 16. In summary, 3xTg-AD mice showed exploratory and recognition memory impairments, early hippocampal structural loss, increased Aβ and hyperphosphorylated tau and decreased levels of taurine. In sum, the 3xTg-AD animal model mimics pathological and neurobehavioral features of AD, with early-onset recognition memory loss and MRI-documented hippocampal damage. The early-onset profile suggests temporal windows and opportunities for therapeutic intervention, targeting endogenous neuroprotectors such as taurine.

The aim of the present study was to develop a fully-automated computational solution for computer-aided diagnosis in Parkinson syndrome based on [(123)I]FP-CIT single photon emission computed tomography (SPECT) images. A dataset of 654 [(123)I]FP-CIT SPECT brain images from the Parkinson's Progression Markers Initiative were used. Of these, 445 images were of patients with Parkinson's disease at an early stage and the remainder formed a control group. The images were pre-processed using automated template-based registration followed by the computation of the binding potential at a voxel level. Then, the binding potential images were used for classification, based on the voxel-as-feature approach and using the support vector machines paradigm. The obtained estimated classification accuracy was 97.86%, the sensitivity was 97.75% and the specificity 98.09%. The achieved classification accuracy was very high and, in fact, higher than accuracies found in previous studies reported in the literature. In addition, results were obtained on a large dataset of early Parkinson's disease subjects. In summation, the information provided by the developed computational solution potentially supports clinical decision-making in nuclear medicine, using important additional information beyond the commonly used uptake ratios and respective statistical comparisons. (ClinicalTrials.gov Identifier: NCT01141023).

Deficits in mitochondrial function and redox deregulation have been attributed to Huntington's disease (HD), a genetic neurodegenerative disorder largely affecting the striatum. However, whether these changes occur in early stages of the disease and can be detected in vivo is still unclear. In the present study, we analysed changes in mitochondrial function and production of reactive oxygen species (ROS) at early stages and with disease progression. Studies were performed in vivo in human brain by PET using [⁶⁴Cu]-ATSM and ex vivo in human skin fibroblasts of premanifest and prodromal (Pre-M) and manifest HD carriers. In vivo brain [⁶⁴Cu]-ATSM PET in YAC128 transgenic mouse and striatal and cortical isolated mitochondria were assessed at presymptomatic (3 month-old, mo) and symptomatic (6–12 mo) stages. Pre-M HD carriers exhibited enhanced whole-brain (with exception of caudate) [⁶⁴Cu]-ATSM labelling, correlating with CAG repeat number. Fibroblasts from Pre-M showed enhanced basal and maximal respiration, proton leak and increased hydrogen peroxide (H₂O₂) levels, later progressing in manifest HD. Mitochondria from fibroblasts of Pre-M HD carriers also showed reduced circularity, while higher number of mitochondrial DNA copies correlated with maximal respiratory capacity. In vivo animal PET analysis showed increased accumulation of [⁶⁴Cu]-ATSM in YAC128 mouse striatum. YAC128 mouse (at 3 months) striatal isolated mitochondria exhibited a rise in basal and maximal mitochondrial respiration and in ATP production, and increased complex II and III activities. YAC128 mouse striatal mitochondria also showed enhanced mitochondrial H₂O₂ levels and circularity, revealed by brain ultrastructure analysis, and defects in Ca²⁺ handling, supporting increased striatal susceptibility. Data demonstrate both human and mouse mitochondrial overactivity and altered morphology at early HD stages, facilitating redox unbalance, the latter progressing with manifest disease.