J of Nuclear Medicine Technology, first published online September 3, 2015 as doi:10.2967/jnmt.115.162404 A compound for use in imaging procedures Original research article Mulugeta Semework, Ph.D., Postdoctoral Research Scientist Columbia University Department of Neuroscience 1051 Riverside Drive, Unit 87 New York, N.Y. 10032 e-mails: [email protected] [email protected] Tel: 678-362-3554, Fax: 646-774-7649 Sources of support: NINDS training grant from 2T32MH015174-35 (to Dr. Rene Hen); Support from NEI grant 1 R01 EY014978-06 (to Dr. Michael E. Goldberg); Supplement grant through NEI grant 3 R01 EY014978-06; Brain & Behavior Research Foundation (NARSAD) 2013 Young Investigator Award; generous scan time, technical and expert support from New York State Psychiatric Institute MRI unit, PET Center at Columbia University Medical Center Department of Radiology, Department of Radiology of the Center for Neurobiology and Behavior, of Columbia University/Neurological Institute and the radiology department of NY- Presbyterian Hospital. Word count: 5073 (including references) Short running title: Imaging compound 1 Abstract Numerous research and clinical interventions, such as targeted drug deliveries or surgeries, finding blood clots, abscess, lesions, etc., require accurate localization of various body parts. Individual differences in anatomy make it hard to use typical stereotactic procedures that rely upon external landmarks and standardized atlases. For instance, it is not unusual to make misplaced craniotomies in brain surgery. This project was thus carried out to find a new and easy method to correctly establish the relationship between external landmarks and medical scans of internal organs, such as specific brain regions. METHODS This paper introduces an MRI, CT scan and X-ray visible compound (composition) that can be applied to any surface and therefore provide an external reference point to an internal (eye-invisible) structure. RESULTS Tested in non-human primates and isolated brain scans, this compound showed up with the same color in different scan types, making practical work possible. Conventional, and mostly of specific utility products such as contrast agents, are differentially colored or completely fail to show up, and are not flexible. CONCLUSION This composition can be made with different viscosities, colors, odor, etc. It can also be mixed with hardening materials such as acrylic for different uses, such as for industrial/engineering objectives. Laparoscopy wands, electroencephalogram (EEG) leads, etc. could also be embedded with or surrounded by the compound for ease in 3D visualizations. A pending US patent (IR# CU13187) endorses this invention. 2 Keywords— Structural MRI, CT-scan, X-ray, imaging compound, neurosurgery. 3 I. INTRODUCTION Medical and engineering practices constantly employ the use of devices and methods for visualizing internal structures in humans, animals, machines, etc. Three very well established imaging methods, magnetic resonance imaging (MRI), computed tomography (CT) and X-ray are commonly employed. Recently, integrated Positron emission tomography (PET) magnetic resonance (PET/MR) systems have been getting attention and are currently being used in the clinic to measure motion with high temporal resolution (1) without additional instrumentation. The question still remains, how can one externally register a MRI, CT, or X-ray identified internal body part with those visible to the naked eye? For instance, where should a surgeon make a precise 2 cm skin incision to remove a bone outgrowth which is only 1 cm wide, if that is all he needs? With its increased ease, power and accessibility, especially the high resolution of T1-weighted structural images (2), MRI continues to be the choice medical imaging technique. There has been a growing interest in using this tool to study brain structure, function, development, and pathologies (3). However, unresolved technical and scientific difficulties, such as lack of means to scan and visualize certain objects, make it difficult to match up interest with success. These problems are critical especially when one considers surgery on vital structures such 1 as the brain, as anatomy differs despite similarities in organization and relative location with respect to each other. There is variability between individuals in pattern of brain area folding, shape and size of cortical areas and relative locations (4). It is not uncommon to make a misplaced craniotomy when standardized atlases are used for localization of subcortical neural regions (5). Since MRI is a non-invasive method that capitalizes on the complex mosaic across the cortical sheet (4), and since it permits the visualization of the neural structure of the brain in vivo (5), it is possible to solve much of this problem by taking individual MRIs pre-surgery and mapping structures of interest to an external marker and using established coordinates during surgery. This invention aims at contributing to such a solution by expanding on a recent knowledge gained from preliminary research on non-human primates. It also builds upon an old method developed for expressing relationships between surface markers, such as tattoos on head skin and underlying major brain structures (6). The previous (old) method mentioned above used a common practice of land marking to form a mathematical mapping with internal structures of interest. Skin tattoos (outside markers) were identified in MRI scans from vitamin E tablets affixed to the skin overlaying the tattoos. This posed three major problems for a wider use: 1) Vitamin E doesn’t show up equally and clearly in CT and X-ray scans and several MRI sequences, such as T1, T2 and flairs. 2) The tablets are not flexible and sizable to affix to different external body parts which are not always straight or easily 2 accessible. 3) Not all external body parts that are accessible and straight allow reliable contact (stickiness) with the tablets. The aforementioned problems call for a flexible, sizable and safe substance which can be used in, if not all, several MRI sequences and other scanning methods. This paper introduces such a substance, an imaging compound which is not available in the market. II. MATERIALS, METHODS AND PRELIMINARY RESULTS To replicate common problems, such as Vitamin E and Gd showing up only on certain scans and conditions, data from both the starting development process and the final stages are presented in this and the main results section. In short, the compound has been tested in monkey MRI, and fixed monkey brain CT scans and X-rays and it has been found to have well delineated radio density. It has not been clinically tested. For all experiments, there was no human subjects used and therefore no need for Institutional Review Board approval. The Animal Care and Use Committees at Columbia University and the New York State Psychiatric Institute (NYSPI) approved all protocols as complying with the guidelines established in the Public Health Service Guide for the Care and Use of Laboratory Animals. Figure 1 shows initial testing results in brief. The ingredients and the final mix were separately packed into different compartments of a small multi-pocketed plastic pouch. The compound (mix) is the only formulation which shows up more or 3 less equally and clearly in T1, T2 and T2 flair MRI scans (see Table 1 for parameters for all MRI sequences). In general laboratory research practices, non-human primate skulls are routinely covered with a dental acrylic (cement), either to protect a craniotomy or to secure a head-posting structure. Being an ‘inert’ structure, the dental acrylic cannot be seen in any MRI scan. Using the compound however, its outlines can now be visualized. This allows the acrylic mound to be used in planning future surgeries, or following up of any process and objects inside it, or inside the brain (Figure 2). By extension, the compound can be put over any body part, such as the skin over a patient’s chest, neck, etc. and the scan results can be used to plan interventions. Since ultimately clinical utility will be the greatest target, the final MRI testing of this product was performed in a setting which resembles common medical practices in two ways. One: MRI scanning sequences with parameters used in patient evaluation procedures, including T1, T2, fast-spin echo (FSE), Fractional anisotropy, single-shot FSE (SSFSE), three-dimensional Fast Spoiled Gradient Echo (3D-FSGPR), etc. were implemented. Two: a number of small vinyl tubes filled with the compound were glued to a plastic helmet (a swimming cap that mimics EEG caps, as shown in Figure 3), and the aforementioned scans were acquired. This is to demonstrate one possible use: a multi-purpose wearable landmark that can be imaged overlaying body parts (brain structures for instance). Shown in Figure 3 are the results from an assortment of scans of the compound in a network of surgical tubes glued to a plastic cap covering a phantom/dummy brain. Note that the scans that do not show the compound clearly 4 are where diffusion and anisotropy are imaged, ones that are not the most widely used in the clinic. However, the seemingly negative results in Figure 3 were mostly because the parameters for all the scans have not been optimized at this stage. Further refinement (of the MR methods and the chemistry of the compound) resulted in more positive results (subsequent figures). The compound’s constitution was modified for the second round of testing, which aimed at further ascertaining the preliminary results and including other MRI sequences and scan types (CT and X-ray). The main ingredients and their proportions (by volume) are: 1) distilled water/Betadine: 30- 45%, as solvents and bright T2-weighted MR images; 2) vitamin E oil: 15-20%; 3) purified butter: 5-10%; 4) Olive Oil (slightly warmed) 5-10%; 5) other materials specific to project particulars (up to 15%). Based on desired consistency and purpose, the percentage of the ingredients can be modified to make the compound.