Substantia. An International Journal of the History of Chemistry 2(2): 73-80, 2018 Firenze University Press www.fupress.com/substantia ISSN 1827-9635 (print) | ISSN 1827-9643 (online) | DOI: 10.13128/substantia-61 Citation: V. Lusa, A. Franza (2018) Visualizing Chemistry. The Application of Chemical Imaging to Address Sci- entific Challenges in Space Research. Substantia 2(2): 73-80. doi: 10.13128/ substantia-61 Copyright: © 2018 V. Lusa, A. Franza. This is an open access, peer-reviewed article published by Firenze University Press (http://www.fupress.com/substan- tia) and distribuited under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All rel- evant data are within the paper and its Supporting Information files. Competing Interests: The Author(s) declare(s) no conflict of interest. Research Article Visualizing Chemistry. The Application of Chemical Imaging to Address Scientific Challenges in Space Research Vincenzo Lusa1, Annarita Franza*2 1 JD, Pontificia Università San Bonaventura, Via del Serafico, 1 - 00142 Rome (Italy) 2 PhD, Dipartimento di Scienze Biomediche, Sperimentali e Cliniche “Mario Serio”, Uni- versità di Firenze, Largo Brambilla, 3 - 50134 Florence (Italy) E-mail: viclusa@libero.it; annarita.franza@gmail.com Abstract. Chemical Imaging helps to answer difficult questions, especially when those questions occur in complex environments. For instance, forensic neuroradiology plays an important role in the courtroom to understand a defendant’s personality. But could this branch of science be essential in human exploration of space? Even if no emergen- cy has happened so far, NASA established a partnership in 2002 with the U.S. National Institute of Justice to promote the knowledge of investigative techniques in the case of a crime being committed on a space mission. Based on forensic neuroradiology and behavioral genetics, this article presents a brand-new study protocol for creating security procedures designed to safeguard astronauts engaged in long-duration space travel. Since 2009 in Italy, some individuals have been prosecuted who, although con- victed of murder, benefitted from reduced sentences through the verification of some genetic polymorphisms and Computed Axial Tomography (CAT), Positron Emission Tomography (PET), and functional Magnetic Resonance Imaging (fMRI) results which showed brain malformations that may produce manifestations of violence. The proto- col specifically uses chemical imaging and behavioral genetics to show how cerebellar anomalies and biological markers predictive of criminal behavior can trigger impulsive reactions in response to stress. This protocol may prove critical when space agencies are evaluating candidates for extra-orbital flights of long duration. Keywords. Chemical imaging, forensic radiology, NASA, behavioral genetics, space research. INTRODUCTION In 1958, President Eisenhower proposed creating a civilian space agency for the United States. After considerable congressional debate, the National Aeronautics and Space Administration (NASA) began its opera- tions on October 1, 1958. No one could ever have foreseen what would occur over the next 50 years as humans discovered that the sky was no longer a limit and it is now about to enter a new era of space exploration with a 365-day stay on the ISS, the establishment of a lunar landing out- 74 Vincenzo Lusa, Annarita Franza post, and the future missions to Mars and to a near- Earth asteroid (NEA).1,2 As missions to NEA and Mars are not just ordinary space flights, the analysis of physiological and psycho- logical risk factors of past missions will not be relevant bases for predicting the risk factors astronauts may encounter during space flights.3 At the Hawaii Space Exploration Analog and Simulation center, NASA con- cluded in 2016 a year-long study regarding the use on a shuttle of the forensic sciences utilized in examining crime scenes.4 In fact, the probability of criminal con- duct in space is not so remote. For instance, astronauts have carried weapons into space since the Soyuz flights in 1965.5 Thus, forensic scientists are prepared to face the eventuality of assessing crime scenes and identifying evidence during space travel. So it is no coincidence that NASA established a partnership with the U.S. National Institute of Justice to implement investigative techniques for use in future crime scenes in space.6 Over the last two decades, several studies have been published regarding the impact of long-duration space flight on the health of crewmembers.7 Moreover, while the physiological effects of space flight are well docu- mented,8 a paucity of knowledge exists on the potential behavioral and cognitive issues that can affect the astro- naut’s psychophysical performance during flights. For instance, the neurobiological consequences of long-dura- tion space flight and long-term exposure to microgravity can lead to alterations in cerebral morphology (e.g. the Visual Impairment and Intracranial Pressure Syndrome) that are poorly understood.9.10 Even if no emergency has happened so far, we need to think the unthinkable: how would we deal with a cat- astrophic scenario during a long-duration space flight? In this paper, we present a study protocol that aims at certain security procedures designed to safeguard astro- nauts engaged in long-duration space travels. The pro- tocol is based both on chemical imaging, e.g. forensic neuroradiology, to evaluating the cerebral regions whose anomalies can lead to antisocial behaviors,11 and on behavioral genetics where it has been demonstrated how specific predictive biomarkers of criminal behavior can lead to an unpredictable response in very stressful situ- ations.12 These evaluations can be crucial for space agen- cies at a time in which space tourism is going to become an achievable dream.13 MATERIALS AND METHODS NASA’s Human Research Program has identi- fied 32 space-related health risks associated with space f light and has listed them in the Human Bioastro- nautics Roadmap. The level of risk refers to three specific parameters: a 1-year tour of duty on the ISS, a month- long stay on the moon, and a 30-month mission to Mars. Health risk factors are then categorized into: (1) behav- ioral health and performance; (2) human health counter- measures (e.g., bone metabolism and physiology, nutri- tion, immunology, cardiac and pulmonary physiology); (3) space radiation; (4) space human factors and habit- ability; and (5) exploration medical capabilities. The risk factors have been rated as Controlled, Acceptable, Unac- ceptable and Insufficient Data. The Roadmap then high- lights as unacceptable the risk of behavioral issues and psychiatric disorders.14 In 2007, NASA developed various health standards (i.e., Crew Health Concept of Operations and Medical Operations Requirements) directed towards “a healthy and safe environment for crewmembers during all phas- es of space flight”.15 A review of all the NASA health standards is conducted every 5 years or any time new scientific data suggest that an update is needed. In addition to the standards described above, NASA has identified specific health criteria for crew selection including a medical screening and annual examinations reported in the Astronaut Candidate Program and sup- ported by the NASA Aerospace Medicine Board.16 It is worth mentioning that health risk and stressor param- eters may be different from mission to mission. Con- cerning behavioral health and performance risks, NASA has identified three stressors associated with long-dura- tion space flight: (1) adverse behavioral conditions and psychiatric disorders;17 (2) performance errors due to fatigue;18 and (3) performance decrements due to inad- equate cooperation, coordination, communication, and psychological adaptation within a Team Gap.19 These cri- teria were identified by analyzing observational data and experimental studies in analogous settings, such as sub- marine,19,20 space simulations,21 mountain survival pro- grams and polar expeditions.22 It is important to note that behavioral health prob- lems may be underestimated due to the reluctance of crewmembers to report them.23,24 In 2000, a survey documented a 2.86 per person-year incidence of behav- ioral problems among the 508 astronauts engaged in space shuttle flights between 1981 and 1989.25 In 2009, observational information collected for 28.84 person- years described anxiety and irritability as the most common behavioral symptoms (0.832 cases per person- year).26 Furthermore it was pointed out that behavioral health issues are frequent during long-term periods of isolation and confinement.27 A 2004 study reported a 5.2 percent probability of behavioral issues in aspiring 75Visualizing Chemistry. The Application of Chemical Imaging to Address Scientific Challenges in Space Research astronauts after extended stays in Antarctica. Among the most common risk factors of behavioral health problems are mission duration, circadian rhythm disorders and microgravity effects on human physiology, social isola- tion, cultural and organizational issues and personal- ity traits.28 Risk management procedures have focused on providing social and psychological support to crew- members through ground control. However, even if these countermeasures have proved to be effective on the ISS, it is unknown whether they could be useful during long-term space flights at greater distances from Earth.2 Cognitive and psychiatric tests are administered dur- ing both the astronaut enrollment procedures and the annual medical examinations.29 Neurocognitive and behavioral genetic testing have also been developed, but they serve mainly to point out phenotypic and geno- typic variations to manage sleep-wake disruptions dur- ing space missions.30 To date, few policies have been established for long-duration space flights. In analogous settings, the National Science Foundation’s Division of Polar Programs require a psychiatric evaluation con- ducted by a civilian contractor of all aspiring astronauts engaged in winter-over duty at Antarctica’s Amundsen- Scott South Pole and McMurdo stations. Limits have also been placed on the number of continuous seasons a candidate can stay at the same station.29 Astronauts are then informed that ordinary social and personal problems can become clinically significant during peri- ods of extended isolation and confinement. For instance, the Mars Society conducted a 4-month simulated Mars exploration mission at the Flashline Mars Arctic Research Station in 2007. Analyzing the questionnaires that crewmembers completed on five different occasions during the simulation, scientists found an increase in stress factors as well as higher levels of excitement, lone- liness and tiredness. These results thus prompt serious questions about psychological issues during missions to the outer solar system where a mission’s total dura- tion is expected to last 10 years or more (e.g., interstellar travel to the Oort Cloud, a broad spherical shell of comet nuclei located 0.63-0.94 light years away from the Sun).31 These kinds of human expeditions will cause astro- nauts to undergo psychological and interpersonal stress- ors that they have never before experienced, such as an unknown level of monotony and isolation, impossible real-time communication with the Earth, which will even disappear from their view. Such would be the case of missions to Mars where a crew of six or seven people would be on a space flight lasting at least 2.5 years. For the very first time in human history, they would experi- ence the “Earth-out-of-view phenomenon”. Gazing at the Earth has been one of the major positive factors of being in space for astronauts. Its absence could lead crewmem- bers to an increased sense of isolation, emotional insta- bility, hypersensitivity, depressive reactions, and possibly psychiatric disorders.32 As has already been mentioned, many unknown health risks may influence long-duration space flight. In this regard, it is noteworthy to emphasize that chemi- cal imaging can make a positive contribution to foren- sic space research. For instance, a recent clinical survey tested via fMRI the neuronal functions of a 44-year-old male cosmonaut engaged in a long-duration space flight (169 days) on the Russian segment of the ISS. Even if his physical state and performance showed no relevant anomalies, the f MRI scans indicated abnormalities in the vestibular and motor-related cerebral regions.10 Moreover, results from the MARS105 study have shown a deterioration in the astronauts’ psychological state dur- ing a long period of confinement, which was accompa- nied by a decrease in brain cortical activity.33 Again, in a study carried out using low-resolution brain electromag- netic tomography (LORETA), neuropsychiatrists have demonstrated how the microgravity phases of parabolic flights induce changes in frontal lobe activity, a cerebral region that is involved in the regulation of emotional processing.34 Despite what has been described above, the contri- bution of forensic neuroradiology and neurobiology to space research seems to be underestimated. Therefore, increased focus on brain imaging and behavioral genet- ics can lead to the development of adequate counter- measures to safeguard astronauts involved in long-dura- tion space missions Brain imaging Cognitive neurosciences have as a study subject an understanding of the mechanisms that are the basis of human aggressivity; they find their correspondence at an organic level and in particular cerebrally. The main objective of this branch of research is to investigate vio- lent behavior in humans by studying certain cerebral areas using neuroimaging techniques, which constitute a major source of scientific acquisition in the neurocrime field. It follows that cognitive neurosciences, linked to the growing technological development in the field, are destined to evolve over the next few decades influencing such fields as psychiatry, forensic psychology, and crimi- nal law in studying the mens rea.35 The development of multiple imaging techniques provides powerful tools to probe multiple aspects of brain anatomy. New technologies not only allow the study of structural features but also reveal brain con- 76 Vincenzo Lusa, Annarita Franza nectivity, neurotransmitter receptor profiles, and other important aspects of brain function. These sophisticated imaging systems are divided mainly into the following areas: EEG (electroencephalography); CAT (computer- ized axial tomography) scan; functional magnetic reso- nance imaging (f MRI); positron emission tomography (PET); single-photon emission computed tomography (SPECT); and magnetoencephalography (MEG). In detail, EEG allows direct assessment of the brain’s electrophysiology by displaying the temporal and spa- tial pattern of the neuronal populations generating the underlying neuroelectric and neuromagnetic fields. Given its temporal sensitivity, EEG is useful in the evaluation of dynamic cerebral functioning such as suspected sei- zures and unusual spells.36 CAT scan is a computerized X-ray imaging technique where a motorized X-ray source rotates around the circular opening of a gantry, pro- ducing signals that are then processed by the machine’s computer to generate 2-D cross-sectional tomographic images (often called “slices”). The thickness of each slice usually ranges from 1-10 millimeters. When the number of desired slices is collected, image data is recorded in DICOM format and images can be displayed separately or stacked together by the computer to produce high-res- olution 3-D images (c.50μm).37 CAT scan and magnetic resonance imaging (MRI) have allowed for the first time the noninvasive evaluation of brain structure. In particu- lar, f MRI is a modern noninvasive imaging technique to measure and localize specific functions of the human brain without the application of radiation. Indeed, fMRI takes advantages of the differences in magnetic suscep- tibility between oxyhemoglobin and deoxyhemoglobin. When a task is performed, oxygenated blood in excess of the amount needed (luxury perfusion) is delivered to the active area. The difference in magnetic susceptibility between deoxyhemoglobin concentrations and oxyhemo- globin concentrations creates the signal in functional imaging. Brain function is indirectly assessed with high spatial resolution via detection of local hemodynamic changes in capillaries and draining veins of the so-called functional areas, e.g. regions of the human brain that govern motor, sensory, language, or memory functions. Thus, f MRI not only offers a variety of novel options for research but also opens up a new diagnostic field of neuroradiology, by shifting paradigms from strictly mor- phological imaging to measurement and visualization of brain function.38 Other frequently applied methods for the identification of functionally important brain structures are PET and SPECT, which detect changes of cerebral blood flow and glucose metabolism. Most sig- nificantly, PET measures generally reflect the functional biochemistry and physiology of the brain. This is accom- plished by injecting radioactive isotopes that have short half-lives. Isotopes used frequently in PET research allow a variety of radiochemical approaches to ligand synthesis. Of particular importance, isotopes of carbon and nitro- gen may be directly incorporated, and 18F can be sub- stituted for hydrogen or a hydroxyl substituent in many compounds without loss of bioactivity. Blood flow indeed increases in areas of the brain that are in heavy use and a fair portion of the injected isotopes will end up in the active part of the brain. As the isotopes decay, a positron is released. This positron will collide with an electron and they will annihilate each other, sending two photons, or γ-rays, in opposite directions. These γ-rays are picked up by the PET scanner, which then determines where they came from the brain. Tomographic techniques analogous to those utilized in CAT scanning, are used to reconstruct the image from the rays. The resulting PET images are spatial maps of radioactivity distribution within tissue slices.39 SPECT is another nuclear imaging technique for imaging molecules, metabolisms, and bio- chemical functions of organs and cells, and like PET, the use of radioisotopes is required. As its name suggests, it involves the emission of a single γ-ray per nuclear disin- tegration, which is measured directly. Numerous single γ-rays are detected by rotating gamma cameras to recon- struct an image of the origin of the γ-rays, which identi- fies the location of the radioisotope. Before a test is per- formed, the patient is injected with a radiopharmaceu- tical that emits γ-rays and can be detected by the scan- ner. The most common radioisotopes used in SPECT are Iodine-123, Technetium-99m, Xenon-133, Thallium-201, and Fluorine-18. SPET scan is primarily used to measure the regional cerebral blood flow. One of its major advan- tages is that SPECT provides improved contrast between regions of different functions, and also give better spa- tial localisation and greater accessibility because it uses radioisotopes with longer half-lives.40 Finally, MEG is the measure of magnetic fields generated by the electrical activity of neurons. When neurons are activated synchro- nously they generate electric currents and thus magnetic fields, which are then recorded by MEG outside the head. Once generated, magnetic fields are relatively invulner- able to intervening variations in the media they traverse, so they are not distorted by the skull, grey and white matter, and cerebrospinal fluid. But these neuromagnet- ic signals are extremely small, about 10−15 T. Thus, MEG scanners require superconducting quantum interference device (SQUID) sensors. To detect and amplify the mag- netic fields, the SQUID sensors are bathed in a large liq- uid helium cooling unit at about -270°C. A magnetically shielded room houses the equipment and mitigates inter- ference.41 77Visualizing Chemistry. The Application of Chemical Imaging to Address Scientific Challenges in Space Research The brain areas that are relevant to the present study are the amygdala, hippocampus, thalamus, midbrain, and prefrontal cortex. The amygdala is involved in pred- atory and affective attacks. The thalamus connects the limbic emotional areas and cortical areas. When acti- vated, the midbrain manages impulsive aggression due to emotions.42 The literature has found that reduced hip- pocampal function can be associated with high levels of psychopathy.43 The hippocampus also plays a primary role in fear conditioning and in emotional responses.44 The almond-shaped amygdala is also involved in the generation of emotions. An amygdala dysfunction leads to manifesting impulsive, even violent behaviors.45 For instance, a decrease in the amygdala’s volume equal to 18% can instead be the basis of sociopathic behaviors.46 As regards the midbrain, a disorder in the posterior cin- gulate cortex can trigger anger. In addition, it distorts the possibility of understanding how this behavior can influence others.47 The same applies to the anterior cin- gulate, the cerebellar anatomical region designated to inhibit automatic and instinctive behaviors and to regu- late instinctive reactions.48,49 The most important evidence capable of translat- ing into reality the literature attesting to the biologi- cal nature of the anti-social acts is found in the judicial practice of both Italian and US criminal trials, where a reduced sentence was imposed on the basis of the con- firmation of anatomical differences in the defendant’s brain as well as genetic anomalies that were capable of influencing the behavior of individuals, causing them to carry out heinous behaviors against their fellow humans. US criminal trials The use of bioscience in criminal cases dates back to the early 1980s when chemical imaging and behavio- ral genetic evidence began to enter US courtrooms. On March 30, 1981, John Warnock Hinckley Jr. shot Presi- dent Ronald Regan six times, also critically wounding police officer Thomas Delahanty, Secret Service agent Timothy McCarthy, and Reagan’s press secretary, James Brady. When he was put on trial for his crimes, Hinck- ley was found not guilty by reason of insanity and con- fined to St. Elizabeth’s mental hospital in DC. He was released in September 2016. The Hinckley case revo- lutionized the US criminal justice system introducing CAT scans as a useful tool for proving mental incapac- ity. The psychiatric David Bear explained to the jury that the defendant’s brain scans indicated that Hinck- ley’s sulci were wider than average, a feature that he had noticed in patients suffering from schizophrenia. The CAT scans bolstered Bear’s diagnosis of mental insanity and the jury agreed that Hinckley was mentally incapa- ble of understanding the crimes he had committed.50 In 1991, while engaged in a heated argument, Her- bert Weinstein strangled his wife Barbara and then tried to cover the murder up by throwing her body from the window. Before the trial began, and because he had no history of violent behavior, Weinstein had an MRI fol- lowed up with a PET scan. Exams revealed an anomaly in Weinstein’s prefrontal cortex and an arachnoid cyst growing in his left frontal lobe. These findings showed how the defendant was not able to control his aggressive behavior in a very stressful situation and thus he was found not criminally responsible due to mental defect.51 On October 18, 1992, Johnny Hoskins was arrested for having raped, beaten and strangled Dorothy Berger, an 80-year-old who lived in Brevard County, Florida. He was sentenced to death on April 4, 1994. Seven months later, Hoskins filed a Direct Appeal with the Florida Supreme Court (FSC), claiming that the trial judge had improperly barred neurological testing. Upon review, the FSC affirmed Hoskins’s convictions, but remanded him to the State Circuit Court for a PET scan. Results showed Hoskins as having frontal lobe lesions and thus a lack of control of his inhibition restraints. Consequent- ly, the FSC vacated the death sentence.52 In March 2010, Brian Dugan was admitted to Northwestern Memorial Hospital in Chicago to have an f MRI and a series of cognitive, attention and moral decision-making tests. In 1983, Dugan had kidnapped, raped, and beaten to death 10-year-old Jeanine Nica- rico. One year later, he raped a 27-year-old nurse and drowned her in a quarry. In 1985, he kidnapped, raped, and killed a 7-year-old girl. The neuroscientist Kent Kie- hl who concluded that Dugan’s brain suffered from an anomaly in his prefrontal cortex performed neurological testing. Consequently, Dugan was incapable of control- ling his impulses, differentiating right from wrong, and understanding the consequences of his actions. Kie- hl’s report was used to mitigate death penalty charges against Dugan.53 One recent study reported over 1585 cases between 2012 and 2015 in which neuroscience and behavio- ral genetics were reported in a judicial decision in the US criminal justice system. The data collected show an increasing use of neurological testing by the courts, with over 300 decisions in 2012 alone. Neurobiological evi- dence has been introduced in 5-6% of all murder trials and the most common type of brain scanning is MRI or CAT, rather than fMRI or SPECT. The study then high- lights the use of neuropsychological testing and neuro- imaging in pretrial proceedings as an improvement in the evaluation of subjective competency.54 78 Vincenzo Lusa, Annarita Franza Italian criminal trials - The Bayout case In 2007, a forty-year-old Algerian, Bayout was involved in a quarrel in Udine, which erupted into a fight as the defendant usually wore eye make-up for religious reasons and for having been insulted with racial slurs. This led to his stabbing to death the indi- vidual who had provoked him. Sentenced to nine years in prison, the Court of Appeal made arrangements for a genetic test in which anomalies were detected in five of the genes linked to violent behavior, including a gene polymorphism (MAO-A). The court of justice stated that being a carrier of the low-activity allele for the MAOA gene (MAOA-L) would make Bayout more inclined to manifesting impulsive, aggressive behav- ior when provoked or socially excluded (from judgment no. 5-09/18/2009). Namely, he was affected by a kind of “genetic vulnerability” and the presence in the defend- ant’s chromosomal inheritance of certain genes made him “particularly reactive in terms of aggressivity in stressful situations, and even more so if the individual had spent his childhood in a disadvantageous, fam- ily environment” (from sentence no. 5-09/18/2009). For these reasons, the Trieste Court of Justice reduced the sentence by one-third (Trieste (Italy) Court of Assizes Appeal no. 5 09/18/2009). The Albertani case The judge for preliminary investigations at the Como Criminal Court sentenced to twenty years in prison a young woman accused and found guilty of kill- ing her forty-year-old sister. Besides also strangling her mother to death, she had tried to destroy the corpse by burning it. Simultaneous to the sentence being pro- nounced, a partial mental defect of the killer came to the judge’s attention because of the results of specific neuroscientific tests intended to ascertain whether the woman presented those alleles significantly associated “with an increased risk of impulsive, aggressive and vio- lent behavior” (from judgment 05/05/2011 no. 536). Dur- ing the trial, the judge established the presence, through biological testing, of some unfavorable alleles present in the defendant’s genetic inheritance, such as the low- activity MAO-A allele, SCL6A4 (STin2 polymorphism) and COMT (rs4680 polymorphism), with the sentence later essentially being reduced. High-resolution brain- imaging techniques (Voxel-based morphometry), were also used in the Como case, which proved how it was possible to make a definite correlation between anoma- lies in certain sensitive areas of the brain and the young murderer’s antisocial actions, particularly, in the wom- an’s brain where abnormally dense gray matter was found in the anterior cingulate. As a matter of fact, the test showed that the volume of gray matter mentioned above, in the anterior cingulate gyrus, turned out to be different from that in a control group of ten healthy women. It is noted that the previously mentioned cere- bellar anatomical region is intended to inhibit automatic and instinctive behaviors. Moreover, in critical situa- tions, it regulates aggressive reactions as well as mendac- ity (Como (Italy) Court, judgment 05/05/2011 no. 536).55 RESULTS AND DISCUSSION If we further examine the risks listed by NASA for the space voyages completed so far, it seems incontro- vertible to state that all kinds of possible emergencies can indeed take place in space. Some of these contin- gencies are known, while others are currently unknown. Indeed, the high degree of stress to which the astro- nauts could find themselves subjected could promote the gradual development of uncontainable stress in individuals whose genetic makeup contains particular polymorphisms or structural abnormalities in the brain that could lead an antisocial behavior being manifested. The protocol presented here is based on forensic neu- roradiology and will have to be implemented together with the psychological and aptitude tests that are usu- ally used in astronaut selection. Therefore it should con- sider, for maximum crew safety the genetic profile and brain anatomy of the candidates and in particular: 1) an examination of those brain structures involved in controlling aggressive impulses and possible anatomical malformations including the telencephalon and cerebral cortex on which the limbic system is present; 2) a study of some alleles that enable understanding the relation- ship between genetics and crime. In fact, the protocol should be based on examining those brain structures involved in controlling aggressive impulses and any ana- tomical defects inherent in the telencephalon in which the limbic system is present. Examinations must also be performed on the hypothalamic-pituitary-adrenal axis, (involved in the control and adaptation to stress) as well as on the connections between the limbic system (the seat of emotions) and the prefrontal cortex (control over impulses including aggressive ones) by using chemical imaging such as functional neuroimaging techniques that study brain function based primarily on measuring blood flow (f MRI), (SPECT), and glucose metabolism (PET) in different areas of the brain. Voxel-based mor- phometry (VBM) shows anatomical connections in the brain as well as the density of gray matter composed of 79Visualizing Chemistry. The Application of Chemical Imaging to Address Scientific Challenges in Space Research neurons and of white matter that instead forms axons. Using this technique, anomalous structures in the brain can be highlighted – something that proved valuable in the Como court case discussed here. The protocol then focuses on examining some of the biomarkers genetically predictive of criminal behavior. For example, regarding the polymorphisms mentioned here, the aspiring astronaut will have to have evaluated and monitored the monoaminergic system to determine the presence of the shorter MAO-A variant (on the X chromosome) in the polymorphic version of MAOA-L as well as the catechol O-methyltransferase (COMT) to confirm the Val158met polymorphism in the COMT. Regarding the serotonergic system, the SCL6A4 gene must be monitored as it is able to reduce aggressive behavior in humans that codes for the serotonin trans- porter (SERT), a key modulator of serotonergic trans- mission. The possible detection of reduced serotonergic activity in the brain may result in increased impulsive and aggressive behaviors via the “s” polymorphism of the SCL6A4 gene, whose existence involves a greater ina- bility to adapt in unfavorable environmental conditions. The dopaminergic system will also be subject to care- ful study as, for example, the SLC6A3 gene (dopamine transporter) has been linked to extremely violent impul- sive-aggressive and antisocial behaviors in an individual whose SLC6A3 gene is found to have the 10 allele. CONCLUSIONS The ability to image the interior of the human body with techniques with chemical imaging has revolution- ized medical diagnosis and treatment. Clearly it appears evident that chemical imaging, forensic neuroradiol- ogy and behavioral genetics are able to produce inno- vations and undoubted benefits to the delicate task of understanding an individual’s true personality. In fact, this research was able to show the validity of the appli- cation of chemical imaging to such an unusual forensic research field as that of space exploration. REFERENCES 1. S.J. Dick, NASA’s first 50 years: historical perspectives. U.S. Government Printing Office, Washington, 2009. 2. J. Kahn, C.T. Liverman, M.A. McCoy, Health stand- ards for long duration and exploration space flight, National Academies Press, Washington, 2014. 3. N. Kanas, Acta Astronaut. 2014, DOI 10.1016/j.act- aastro.2014.06.026 4. P. Wu, J. Morie, P. Wall, T. Ott, K. Binsted, Procedia Eng. 2016, DOI 10.1016/j.proeng.2016.08.132 5. A.I. Skoog, I.P. Abramov, A.Y. Stoklistky, M.N. Doo- dnik, Acta Astronaut. 2002, DOI 10.1016/S0094- 5765(02)00092-9 6. J.I. Trombka, J. Schweitzer, C. Selavka et al., Forensic Sci Int. 2002, DOI 10.1016/S0379-0738(02)00079-8 7. V.S. Kokhan, M.I. Matveeva, A. Mikhametov, A.S. Shtemberg, Neurosci Biobehav Rev. 2014, DOI 10.1016/j.neubiorev.2016.10.006 8. N. Kanas, Acta Astronaut. 2011, DOI 10.1016/j.act- aastro.2010.04.012. 9. K. Marshall-Bowman, M.R. Barrat, C.R. Gibso, Acta Astronaut. 2013, DOI 10.1016/j.actaastro.2013.01.014 10. A. Demertzi, Van Ombergen, E. Tomilovskaya, B. Jeurissen et al., Brain Struct Funct. 2016, DOI 10.1007/s00429-015-1054-3 11. I.A. Brazil, J.D.M. Van Dongen, J.H.R. Maes, R.B. Mars, A.R. Baskin-Sommers, Neurosci Biobehav R. 2016, DOI 10.1016/j.neubiorev.2016.10.010 12. S. McSwiggan, B. Elger, P.S. Appelbaum, Int J Law Psychiat. 2017, DOI 10.1016/j.ijlp.2016.09.005. 13. Y.W. Chang, J.S. Chern, Acta Astronaut. 2016, DOI 10.1016/j.actaastro.2016.06.008. 14. Institute of Medicine and National Research Coun- cil, A risk reduction strategy for human exploration of space: A review of NASA’s Bioastronautics Roadmap. The National Academies Press Washington DC, 2006. 15. NASA, Human research program requirements docu- ment, National Aeronautics and Space Administra- tion Johnson Space Center, Huston, 2013, Revision F. 16. NASA, NASA space flight human system standard, Vol. I: Crew Health, NASA-STD-3001, National Aer- onautics and Space Administration Johnson Space Center, Houston, 2007. 17. NASA, Astronaut candidate program, National Aero- nautics and Space Administration Johnson Space Center, Houston, 2013. 18. K.J. Slack, T.J. Williams, J.S. Schneiderman, A.M. Whitmire, J.J. Picano, Evidence report: Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders, National Aeronautics and Space Adminis- tration Johnson Space Center, Houston, 2016. 19. E. Flynn-Evans, K. Gregory, L. Arsintescu, A. Whit- mire, Evidence report: Risk of Performance Decre- ments and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload, National Aeronautics and Space Admin- istration Lyndon B. Johnson Space Center, Houston 2016. 20. L. Landon Blackwell, W.B. Vessey, J.D. Barrett, Evi- dence report: Risk of Performance and Behavioral 80 Vincenzo Lusa, Annarita Franza Health Decrements Due to Inadequate Coopera- tion, Coordination, Communication, and Psychoso- cial Adaptation within a Team, National Aeronautics and Space Administration Lyndon B. Johnson Space Center, Houston, 2016. 21. S.P. Chappell, A.F. Abercromby, M.L. Gernhardt, Acta Astronaut. 2013, DOI 10.2514/6.2013-3508. 22. C. Strewe, B.E. Crucian, C.F. Sams, et al., Brain Behav Immun. 2015; 10.1016/j.bbi.2015.06.017. 23. J.W. Norbury, W. Schimmerling, T.C. Slaba, et al., Life Sci Space Res. 2016, DOI 10.1016/j.lssr.2016.02.001. 24. L.A. Palinkas, P. Suedfeld P, Lancet. 2008, DOI 10.1016/S0140-6736(07)61056-3 25. Institute of Medicine, Safe passage: Astronauts care for exploration missions, National Academy Press, Washington, DC, 2001. 26. M. Shapanek, Aviat Space Env Med. 2005,76, B25-30. 27. Institute of Medicine (US) Committee on Creating a Vision for Space Medicine During Travel Beyond Earth Orbit, Safe Passage: Astronaut Care for Explora- tion Missions, National Academies Press, Washington DC, 2001. 28. K Cassady, V. Koppelmans, P. Reuter-Lorenz et al., Neuroimage. 2016, DOI 10.1016/j.neuroim- age.2016.07.029 29. L.A. Palinkas, F. Glogower , M. Dembert et al., Int J Circumpolar Health. 2004, 63. 157-168. 30. J. Brcic, Acta Astronaut. 2010, DOI 10.1016/j.actaas- tro.2010.06.044 31. L.S. Bishop, R. Kobrick, M. Battler, Acta Astronaut. 2010, DOI 10.1016/j.actaastro.2009.11.008 32. N. Kanas, D. Manzey, Space Psychology and Psychia- try, El Segundo California and Springer, Dordrecht, 2008. 33. G.G. De La Torre, B. Van Baarsen, F. Ferlazzo, et al., Acta Astronaut. 2012, DOI 10.1016/j.actaas- tro.2012.08.013. 34. S. Schneider, V. Brummer, H. Carnahan et al., Neuro- image. 2008, DOI 10.1016/j.neuroimage.2008.06.010 35. F.A. Elliot, Arch Neurol. 1992, 49, 595-603. 36. J.W. Britton, L.C. Frey, J.L. Hopp et al., Electroenceph- alography (EEG): An Introductory Text and Atlas of Normal and Abnormal Findings in Adults, Children, and Infants, American Epilepsy Society, Chicago, 2016. 37. A.C. Mamourian, CT Imaging. Practical Physics, Arti- facts and Pitfalls, Oxford University Press, New York, 2013. 38. S. Ulmer, O. Jansen, fMRI. Basics and Clinical Appli- cations, Springer, Berlin, 2013. 39. G.J. Siegel, B.W. Agranoff, R.W. Albers et al., Basic Neurochemistry: Molecular, Cellular and Medical Aspects, Lippincott-Raven, Philadelphia, 1999. 40. R.L. Van Heertum, R.S. Tikofsky, M. Ichise, Function- al Cerebral SPECT and PET Imaging, Lippincott Wil- liams & Wilkins, Philadelphia, 2009. 41. P.J. Uhlhaas, P. Liddie, D.E.J. Linden et al., Biol Psy- chiatry Cogn Neurosci Neuroimaging 2017, DOI 10.1016/j.bpsc.2017.01.005 42. A.J. Reiss, K.A. Miczek, J.A. Roth, Understanding and Preventing Violence: Volume 2. Biobehavioral influ- ences. Panel on the Understanding and Control of Vio- lent Behavior, Committee on Law and Justice, National Research Council, National Academy Press, Washing- ton DC, 1994, pp. 59-172. 43. H. Soderstrom, M. Tullberg, C. Wikkelsö et al., Psy- chiatry Res. 2000, 98, 29-41. 44. M. Boccardi, R. Ganzola, R. Rossi et al., Hum Brain Mapp. 2010, DOI 10.1002/hbm.20877 45. P. Marchetti, Psicologia e Giustizia, 2012, 12, 1-14. 46. Y. Yang, A. Raine, K.L. Narr et al., Arch Gen Psychiat. 2009, DOI 10.1001/archgenpsychiatry.2009.110 47. K.N. Ochsner, J.S. Beer, E.R. Robertson et al., Neuro- image. 2005, DOI 10.1016/j.neuroimage.2005.06.069 48. A. Raine, Y. Yang, Soc Cogn Affect Neurosci. 2006, DOI 10.1093/scan/nsl033 49. Raine A, Lencz T, Taylor K, Hellige JB, Bihrle S, Lac- asse L et al. Corpus callosum abnormalities in psy- chopathic antisocial individuals. Arch Gen Psychiatry 2003;60(1):1134-42. 50. O.D. Jones, J.D. Schall, F.X. Shen, Law and Neuro- science, Wolters Kluwer Law & Busines, New York, 2014. 51. D. Patterson, M.S. Pardo, Philosophical Foundations of Law and Neuroscience, Oxford University Press, New York, 2016, pp. 69-83. 52. A.R. Beech, A.J. Carter, R.E. Mann, P. Rotshtein, The Wiley Blackwell Handbook of Forensic Neuroscience, Wiley-Blackwell, New York, 2018. 53. M.J. Saks, N.J. Schweitzer, E. Aharoni, K.A. Kiehl, J Empirical Legal Stud. 2014, DOI 10.1111/jels.12036 54. N.A. Farahany, J Law Biosci. 2016, DOI 10.1093/jlb/ lsv059 55. L. De Cataldo Neurburger L., La prova scientifica nel processo penale, Cedam, Padova, 2003, pp. 317-34.