The authors would like to thank Anne Sandman, Keith Nishihara, and Brian Wilfley from Triple Ring Technologies for their contribution in this project. This work is funded by NIH Challenge Grant 5RC1HL100436-0.

1. System setup
<ol>
 <li>Set up the phantom to image at isocenter (i.e. 40-cm from the collimator).</li>
 <li>Set up the DAP Meter to measure X-ray dose in front of the collimator (Figure 4).</li>
 <li>Power on the SBDX system.</li>
 <li>Select the system operating mode. We are currently using a 7" field of view (FOV) with a frame rate of 15fps. The X-ray source peak voltage is set to 80kVp at 9kW X-ray source power. </li>
</ol>
2. Data acquisition
<ol>
 <li>Start data acquisition from the control computer. During data acquisition, detector images are saved into the system memory. The following steps take place in the SBDX system:
 <ol>
 <li>The electron beam scans each focal spot position sequentially in a raster fashion (Figure 5).</li>
 <li>The electron beam hits the transmission target and generates X-rays (Movie 2).</li>
 <li>At each focal spot position, X-ray photons illuminate the detector using a focusing collimator, thus projecting a small portion of the imaging volume onto the detector.</li>
 <li>For each focal spot position, the detector creates one detector image, which is directly stored in the system memory. </li>
 <li>The selected operation mode of 7&#x2019;&#x2019; 15fps provides 71x71 focal spots. Each focal spot position is illuminated for a total of 8 &mu;s. The exposure time must be broken up into 1 &mu;s increments because of the thermal limitations of the X-ray target. Thus, the beam illuminates the target at each focal spot position for 1 &mu;s and moves to the next focal spot position. At a later time, each focal spot is revisited to complete the 8 &mu;s exposure. As one detector image is created for each focal spot illumination, there are a total of 40328 detector images that are acquired and stored into memory in about 60ms. </li>
 </ol>
 </li>
</ol>
3. Image reconstruction
<ol>
 <li>The SBDX is intrinsically a tomosynthesis system, as the object is illuminated under different angles from the source. Any plane within the imaging volume located between collimator and detector can be reconstructed. The following steps illustrate how the partial images are reconstructed into individual planes, or into a composite or plane selected image. In the clinical SBDX system steps 3.2 to 3.4 will be performed in real-time.</li>
 <li>Select the image reconstruction parameters on the reconstruction simulator. </li>
 <li>Run the image reconstruction algorithm. During image reconstruction the algorithm performs the following steps:
 <ol>
 <li>Read each individual detector image.</li>
 <li>Scale the detector images to match the scale of the plane to reconstruct.</li>
 <li>Shift the images according to their focal spot source location and add them to the reconstruction plane (Movie 3).</li>
 <li>Repeat the last two steps for each focal spot location.</li>
 <li>Perform post processing filtering to remove the pattern created by the shift operation.</li>
 <li>At this point, one plane is reconstructed (Figure 6), and the anatomy of our object is visible. </li>
 </ol>
 </li>
 <li>If requested, run the algorithm to create a plane selected image. The algorithm performs the following steps:
 <ol>
 <li>Point 3.2.1 to 3.2.6 are repeated to create the 32 planes necessary for the plane selected image. The planes usually have a spacing of 0.5-mm (Movie 4, Figure 7 and Movie 5).</li>
 <li>For each portion of the image, the plane that contains the object in focus is selected to be part of the final plane selected image (Figure 8 and Movie 6).</li>
 </ol>
 </li>
 <li>If necessary, reposition the phantom to place the heart in the center of the field of view.</li>
 <li>Perform step 2.1 to 3.3 until the phantom is correctly placed inside the field of view.</li>
 <li>Record the dose area product from the DAP meter for this non-equalized image.</li>
</ol>
4. New operation mode file generation for adaptive exposure
<ol>
 <li>Load the previously acquired detector images into the adaptive exposure simulator.</li>
 <li>Select the adaptive exposure algorithm parameters. </li>
 <li>Run the adaptive exposure simulator. The simulator performs the following steps: 
 <ol>
 <li>The target number of photons per detector image is determined based on the user selected threshold.</li>
 <li>For each focal spot position, the number of photons in the detector image is determined. The detector images from that focal spot position are accumulated until either the target number of photons or the maximum of eight rescans is reached (Figure 9).</li>
 <li>As a result we obtain a rescan map detailing how many times each focal spot position is illuminated (Figure 10).</li>
 <li>The rescan map is merged with the operation mode file that is used to run the SBDX system.</li>
 </ol>
 </li>
</ol>
5. Equalized Image acquisition
<ol>
 <li>Load the updated operation mode file into the SBDX system.</li>
 <li>Start data acquisition from the control computer. Data acquisition is performed as detailed in 2.1.1 to 2.1.5. In contrast to the previous acquisition, the X-ray beam is turned on or off at the focal spot positions according to our rescan map. As the total number of illuminations is smaller than in the standard acquisition, the X-ray dose is reduced. </li>
 <li>Record the dose area product measured by the DAP meter.</li>
 <li>Run the image reconstruction algorithm on the newly acquired equalized data as detailed in 3.2 to 3.4.</li>
 <li>The reconstructed equalized image (Figure 11) is displayed.</li>
</ol>
6. Data analysis
<ol>
 <li>Compare the dose measured for the non-equalized images and the equalized images.</li>
 <li>Observe the difference between the equalized and non-equalized reconstructed images. </li>
</ol>
7. Representative results:
Figure 8 and Figure 11 show the comparison between a standard image and an equalized image. Dose measurements with the DAP meter demonstrate a dose saving of 30% in the equalized image using the rescan mask illustrated in Figure 10. 
In addition, equalization is a very effective way to compress dynamic range, giving a more pleasant appearance of the image without the need for post-processing. 
As shown, equalization filtration can be used to save dose. However, equalization can also be used to improve image quality by matching the radiation dose to the non-equalized image by increasing the source power. In this way, the dark regions of the image receive more photons, resulting in reduced image noise. 
<img src="/files/ftp_upload/3236/3236fig1.jpg" alt="Figure 1" /> 
Figure 1. Conventional fluoroscopy system. A conventional system has a single focal spot X-ray source and a large area detector. The patient is positioned close to the detector.
<img src="/files/ftp_upload/3236/3236fig2.jpg" alt="Figure 2" /> 
Figure 2. SBDX system. The SBDX system operates in inverse geometry. A large scanning beam X-ray source illuminates a small area detector. The patient is positioned far from the detector.
<img src="/files/ftp_upload/3236/3236fig3.jpg" alt="Figure 3" /> 
Figure 3. Flow chart of the data acquisition. 1) A non-equalized image of the phantom is acquired. 2) The data is extracted from the disk array. 3) The adaptive exposure algorithm takes this data as input to create an exposure or rescan mask. 4) The rescan mask is combined with the original operating mode in the source control computer. 5) An equalized image of the same phantom is acquired and stored into the disk array. 6) The non-equalized and equalized data sets are extracted from the disk array, and the image reconstruction software reconstructs the different planes of each data set. 7) Both images are the output of the reconstruction software. 8) Both images are displayed.
<img src="/files/ftp_upload/3236/3236fig4.jpg" alt="Figure 4" /> 
Figure 4. System setup. The phantom is placed on the patient table at isocenter between the X-ray source and the detector. A dose area product meter is placed between X-ray source and phantom.
<img src="/files/ftp_upload/3236/3236fig5.jpg" alt="Figure 5" /> 
Figure 5. X-ray source. An electron beam is generated by the electron gun and scans each hole of the collimator in a raster fashion. Starting from one side of the collimator, the beam scans each hole sequentially. At the end of the row, the beam is turned off and positioned at the beginning of the next row, and the scan is started for that row. This way the electron beam scans the entire collimator, 71 by 71 holes are scanned eight times in approximately 60ms.
<img src="/files/ftp_upload/3236/3236fig6.jpg" alt="Figure 6" /> 
Figure 6. Standard reconstructed image. Reconstructed image of our anthropomorphic phantom displaying the heart with iodinated coronary arteries. The image was taken at 7&#x2019;&#x2019; FOV and 15fps, and a single plane at 45cm from the X-ray target was reconstructed.
<img src="/files/ftp_upload/3236/3236fig7.jpg" alt="Figure 7" /> 
Figure 7. Multi-plane reconstruction. Representation of the different reconstructed planes between the collimator and the detector. The blue cones illustrate how the detector images are backprojected into the reconstruction planes.
<img src="/files/ftp_upload/3236/3236fig8.jpg" alt="Figure 8" /> 
Figure 8. Plane selected image. This image is a composition of 32 planes. In contrast to Figure 6, where only the vessels on the selected plane are in focus, every vessel is in focus.
<img src="/files/ftp_upload/3236/3236fig9.jpg" alt="Figure 8" /> 
Figure 9. Equalization filtration steps. As the collimator is scanned (top), the detector receives a varying count rate depending on the opacity of the object (bottom). Each collimator hole is scanned up to eight times (eight rescans). On the first rescan, the focal spots are illuminated sequentially along the row, starting from the left, and the flux is measured for each hole. On the next rescan, the illumination is repeated starting at the beginning of the row. For each focal spot, the counts are added to the previous value. If the total number of counts exceeds a previously set threshold, this hole will not be illuminated on the following rescan. In the current implementation this process is performed offline and leads to the creation of a rescan mask that subsequently will be used to acquire an equalized image. 
<img src="/files/ftp_upload/3236/3236fig10.jpg" alt="Figure 10" /> 
Figure 10. Rescan map generated by the equalization filtration algorithm. Each pixel of this image represents one focal spot of the collimator. The image is therefore 71x71 pixels. The gray level of each pixel represents the number of rescan for that focal spot, from zero (black) to eight (white). We observe that on the right part of the image, the number of rescan is very low. As a result, each of these focal spots will be illuminated only once or twice. This region corresponds to the lung field area of our reconstructed image (Figure 6), where the image is almost saturated because of the low X-ray absorption of this area.
<img src="/files/ftp_upload/3236/3236fig11.jpg" alt="Figure 11" /> 
Figure 11. Plane selected equalized image. This image is the output of the reconstruction algorithm after adaptive exposure. This image has been acquired with the same operating mode 7" 15fps as the standard image (Figure 8), but with adaptive exposure enabled based on the scan mask of Figure 10. The image is more uniform in terms of intensity, and consequently the vessels appear at higher contrast, especially in dark areas. On the right hand side of the image, there is no longer saturation in the lung field.
Movie 1. Animation of the SBDX system. The SBDX system operates in inverse geometry. A large scanning beam X-ray source illuminates a small area detector. The patient is positioned far from the detector. <a href="https://www.jove.com/files/ftp_upload/3236/3236movie1.swf">Click here to view the movie.</a>
Movie 2. X-ray generation. At each focal spot, the electron beam hits the tungsten target and X-rays are generated. The collimator focuses the X-ray beam toward the detector. <a href="https://www.jove.com/files/ftp_upload/3236/3236movie2.swf">Click here to view the movie.</a>
Movie 3. Image reconstruction animation. This animation represents the process of reconstructing the final image using the detector images. For each focal spot of the collimator (bottom left), the corresponding detector image (upper left) is projected onto the plane to reconstruct (right). In this animation we represent three planes that are being reconstructed at different distances from the X-ray source. <a href="https://www.jove.com/files/ftp_upload/3236/3236movie3.avi">Click here to view the movie.</a>
Movie 4. Plane selection. The SBDX system is a tomosynthesis imaging system. The plane to be reconstructed and visualized can be selected by the user. <a href="https://www.jove.com/files/ftp_upload/3236/3236movie4.swf">Click here to view the movie.</a>
Movie 5. Multi-plane animation. This video shows the different planes reconstructed at increasing distance from the collimator. Notably, the iodinated coronary arteries go in and out of focus depending on their physical location. <a href="https://www.jove.com/files/ftp_upload/3236/3236movie5.avi">Click here to view the movie.</a>
Movie 6. 3D plane selected animation. 3D visualization of the reconstructed focal planes. Focal planes are shifted more with increasing depth. <a href="https://www.jove.com/files/ftp_upload/3236/3236movie6.wmv">Click here to view the movie.</a>

<ol>
	<li>Martinez, L. C., Vano, E., Gutierrez, F., Rodriguez, C., Gilarranz, R., Manzanas, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient+doses+from+fluoroscopically+guided+cardiac+procedures+in+pediatrics.">Patient doses from fluoroscopically guided cardiac procedures in pediatrics.</a> Phys Med Biol. 52, 4749-4759 (2007).</li><li>Strauss, K. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pediatric+interventional+radiography+equipment:+safety+considerations.">Pediatric interventional radiography equipment: safety considerations.</a> Pediatr Radiol. 36, 126-135 (2006).</li><li>Preston, D. L., Cullings, H., Suyama, A., Funamoto, S., Nishi, N., Soda, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Solid+cancer+incidence+in+atomic+bomb+survivors+exposed+in+utero+or+as+young+children.">Solid cancer incidence in atomic bomb survivors exposed in utero or as young children.</a> J Natl Cancer Inst. 100, 428-436 (2008).</li><li>Wolff, M., Keevil, J., Speidel, M., Wilfey, M., Wilfley, B., Star-Lack, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pilot+study+with+a+scanning-beam+digital+x-ray+system.">Pilot study with a scanning-beam digital x-ray system.</a> Am J Cardiol. 94, (2004).</li><li>Speidel, M. A., Wilfley, B. P., Star-Lack, J. M., Heanue, J. A., Betts, T. D., VanLysel, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+entrance+exposure+and+signal-to-noise+ratio+between+an+SBDX+prototype+and+a+wide-beam+cardiac+angiographic+system.">Comparison of entrance exposure and signal-to-noise ratio between an SBDX prototype and a wide-beam cardiac angiographic system.</a> Med Phys. 33, 2728-2743 (2006).</li><li>Speidel, M. A., Wilfley, B. P., Star-Lack, J. M., Heanue, J. A., VanLysel, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Scanning-beam+digital+x-ray+(SBDX)+technology+for+interventional+and+diagnostic+cardiac+angiography.">Scanning-beam digital x-ray (SBDX) technology for interventional and diagnostic cardiac angiography.</a> Med Phys. 33, 2714-2727 (2006).</li><li>Funk, T., Burion, S., Bechtel, K. L., Solomon, E. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> X-ray dose reduction by adaptive source equalization and electronic region-of-interest control. , (2011).</li><li>Burion, S., Bechtel, K. L., Lowell, A. P., Heanue, J. A., Solomon, E. G., Funk, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-time+equalization+filtration:+dose+savings+with+region-based+exposure+control+using+a+scanning-beam+X-ray+source.">Real-time equalization filtration: dose savings with region-based exposure control using a scanning-beam X-ray source.</a> , (2010).</li><li>Boone, J. M., Duryea, J., Moore, E. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Filter+wheel+equalization+in+chest+radiography:+demonstration+with+a+prototype+system.">Filter wheel equalization in chest radiography: demonstration with a prototype system.</a> Radiology. 196, 845-850 (1995).</li><li>Vlasbloem, H., Kool, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=AMBER:+a+scanning+multiple-beam+equalization+system+for+chest+radiography.">AMBER: a scanning multiple-beam equalization system for chest radiography.</a> Radiology. 169, 29-34 (1988).</li></ol>

The authors are employees of Triple Ring Technologies who produce the instrument used in this article.

We demonstrate that dose savings are possible using the equalization technique. In this paper we only show how our technique is applied, without discussing implications for image quality. However, it is important to note that our goal is to maintain a target signal to noise ratio in the equalized images. The underlying assumption is that in non-equalized images, the signal to noise ratio is highly non-uniform. In particular, the bright areas like the lung field exhibit higher signal to noise ratios than necessary to perform the diagnostic task. Equalization allows us to lower the signal to noise ratio in these areas and to maintain signal to noise ratios in the darker regions of the image. We are currently performing noise measurement studies to validate our approach. Preliminary results show that dose savings on the order of 30% are achievable at equivalent signal to noise ratio in the dark regions of the image7, 8.
The potential of equalization filtration has been recognized in the scientific literature for many years. However, so far all published implementations involved mechanical shutters or filters, significantly impeding the utility of this approach9,10. Here we demonstrate that equalization can be based on a fully electronic approach, overcoming the problems with mechanical implementations.
In the clinical SBDX system, most of the steps presented here will be implemented in hardware and will be performed in real time during data acquisition. The equalization algorithm will run in real time, and the displayed image will be equalized by default. The algorithm will dynamically adapt its parameters according to the subject being imaged, the motion of the subject, and the changing gantry position. We continue to improve our algorithm, and further development of our method will be necessary in order to facilitate real-time implementation.

x-ray dose reduction through adaptive exposure in fluoroscopic imaging

X-ray fluoroscopy is widely used for image guidance during cardiac intervention. However, radiation dose in these procedures can be high, and this is a significant concern, particularly in pediatric applications. Pediatrics procedures are in general much more complex than those performed on adults and thus are on average four to eight times longer1. Furthermore, children can undergo up to 10 fluoroscopic procedures by the age of 10, and have been shown to have a three-fold higher risk of developing fatal cancer throughout their life than the general population2,3.
We have shown that radiation dose can be significantly reduced in adult cardiac procedures by using our scanning beam digital x-ray (SBDX) system4-- a fluoroscopic imaging system that employs an inverse imaging geometry5,6 (Figure 1, Movie 1 and Figure 2). Instead of a single focal spot and an extended detector as used in conventional systems, our approach utilizes an extended X-ray source with multiple focal spots focused on a small detector. Our X-ray source consists of a scanning electron beam sequentially illuminating up to 9,000 focal spot positions. Each focal spot projects a small portion of the imaging volume onto the detector. In contrast to a conventional system where the final image is directly projected onto the detector, the SBDX uses a dedicated algorithm to reconstruct the final image from the 9,000 detector images.
For pediatric applications, dose savings with the SBDX system are expected to be smaller than in adult procedures. However, the SBDX system allows for additional dose savings by implementing an electronic adaptive exposure technique. Key to this method is the multi-beam scanning technique of the SBDX system: rather than exposing every part of the image with the same radiation dose, we can dynamically vary the exposure depending on the opacity of the region exposed. Therefore, we can significantly reduce exposure in radiolucent areas and maintain exposure in more opaque regions. In our current implementation, the adaptive exposure requires user interaction (Figure 3). However, in the future, the adaptive exposure will be real time and fully automatic.
We have performed experiments with an anthropomorphic phantom and compared measured radiation dose with and without adaptive exposure using a dose area product (DAP) meter. In the experiment presented here, we find a dose reduction of 30%.

Watch this Scientific Journal Video about X-ray Dose Reduction through Adaptive Exposure in Fluoroscopic Imaging at JoVE.com

X-ray Dose Reduction through Adaptive Exposure in Fluoroscopic Imaging

We are developing a dynamic adaptive exposure technique using our scanning beam digital X-ray system. Rather than exposing an object uniformly, the exposure is adapted depending on the opacity of the object. Here we show an experiment on an anthropomorphic phantom that resulted in a dose saving of 30%.

X-ray fluoroscopy is widely used for image guidance during cardiac intervention. However, radiation dose in these procedures can be high, and this is a ...

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14.3K Views.  Triple Ring Technologies. We are developing a dynamic adaptive exposure technique using our scanning beam digital X-ray system. Rather than exposing an object uniformly, the exposure is adapted depending on the opacity of the object. Here we show an experiment on an anthropomorphic phantom that resulted in a dose saving of 30%.

Video: X-ray Dose Reduction through Adaptive Exposure in Fluoroscopic Imaging

Segmentation and Measurement of Fat Volumes in Murine Obesity Models Using X-ray Computed Tomography

Obesity is associated with increased morbidity and mortality as well as reduced metrics in quality of life.1 Both environmental and genetic factors are associated with obesity, though the precise underlying mechanisms that contribute to the disease are currently being delineated.2,3 Several small animal models of obesity have been developed and are employed in a variety of studies.4 A critical component to these experiments involves the collection of regional and/or total animal fat content data under varied conditions.
Traditional experimental methods available for measuring fat content in small animal models of obesity include invasive (e.g. ex vivo measurement of fat deposits) and non-invasive (e.g. Dual Energy X-ray Absorptiometry (DEXA), or Magnetic Resonance (MR)) protocols, each of which presents relative trade-offs. Current invasive methods for measuring fat content may provide details for organ and region specific fat distribution, but sacrificing the subjects will preclude longitudinal assessments. Conversely, current non-invasive strategies provide limited details for organ and region specific fat distribution, but enable valuable longitudinal assessment. With the advent of dedicated small animal X-ray computed tomography (CT) systems and customized analytical procedures, both organ and region specific analysis of fat distribution and longitudinal profiling may be possible. Recent reports have validated the use of CT for in vivo longitudinal imaging of adiposity in living mice.5,6 Here we provide a modified method that allows for fat/total volume measurement, analysis and visualization utilizing the Carestream Molecular Imaging Albira CT system in conjunction with PMOD and Volview software packages.

Fat content analysis is routinely conducted in studies utilizing murine obesity models. Emerging methods in small animal CT imaging and analysis are providing for longitudinal detail rich fat content analysis. Here we detail step by step procedures for performing small animal CT imaging, analysis, and visualization.

Obesity is associated with increased morbidity and mortality as well as reduced metrics in quality of life.1 Both environmental and genetic factors are ...

Assessing Teratogenic Changes in a Zebrafish Model of Fetal Alcohol Exposure

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States. With 50% of child-bearing age women reporting consumption of alcohol, and half of all pregnancies being unplanned, unintentional exposure is a continuing issue2. In order to best understand the damage produced by ethanol, plus produce a model with which to test potential interventions, we developed a model of developmental ethanol exposure using the zebrafish embryo. Zebrafish are ideal for this kind of teratogen study3-8. Each pair lays hundreds of eggs, which can then be collected without harming the adult fish. The zebrafish embryo is transparent and can be readily imaged with any number of stains. Analysis of these embryos after exposure to ethanol at different doses and times of duration and application shows that the gross developmental defects produced by ethanol are consistent with the human birth defect. Described here are the basic techniques used to study and manipulate the zebrafish FAS model.

In order to understand the molecular mechanisms of the ethanol-induced developmental damage, we have developed a zebrafish model of ethanol exposure and are exploring the physical, cellular, and genetic alterations that occur after ethanol exposure1. We then seek to find potential interventions and rapidly test them in this animal model.

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, ...

Imaging Glioma Initiation In Vivo Through a Polished and Reinforced Thin-skull Cranial Window

Glioma is the one of the most lethal forms of human cancer. The most effective glioma therapy to date-surgery followed by radiation treatment-offers patients only modest benefits, as most patients do not survive more than five years following diagnosis due to glioma relapse 1,2. The discovery of cancer stem cells in human brain tumors holds promise for having an enormous impact on the development of novel therapeutic strategies for glioma 3. Cancer stem cells are defined by their ability both to self-renew and to differentiate, and are thought to be the only cells in a tumor that have the capacity to initiate new tumors 4. Glioma relapse following radiation therapy is thought to arise from resistance of glioma stem cells (GSCs) to therapy 5-10. In vivo, GSCs are shown to reside in a perivascular niche that is important for maintaining their stem cell-like characteristics 11-14. Central to the organization of the GSC niche are vascular endothelial cells 12. Existing evidence suggests that GSCs and their interaction with the vascular endothelial cells are important for tumor development, and identify GSCs and their interaction with endothelial cells as important therapeutic targets for glioma. The presence of GSCs is determined experimentally by their capability to initiate new tumors upon orthotopic transplantation 15. This is typically achieved by injecting a specific number of GBM cells isolated from human tumors into the brains of severely immuno-deficient mice, or of mouse GBM cells into the brains of congenic host mice. Assays for tumor growth are then performed following sufficient time to allow GSCs among the injected GBM cells to give rise to new tumors-typically several weeks or months. Hence, existing assays do not allow examination of the important pathological process of tumor initiation from single GSCs in vivo. Consequently, essential insights into the specific roles of GSCs and their interaction with the vascular endothelial cells in the early stages of tumor initiation are lacking. Such insights are critical for developing novel therapeutic strategies for glioma, and will have great implications for preventing glioma relapse in patients. Here we have adapted the PoRTS cranial window procedure 16and in vivo two-photon microscopy to allow visualization of tumor initiation from injected GBM cells in the brain of a live mouse. Our technique will pave the way for future efforts to elucidate the key signaling mechanisms between GSCs and vascular endothelial cells during glioma initiation.

Imaging Glioma Initiation In Vivo Through a Polished and Reinforced Thin-skull Cranial Window

By combining a polished and reinforced thin-skull (PoRTS) cranial window and glioblastoma (GBM) cell injection, we can observe glioma initiation and growth from injected GBM cells in the brain of a live mouse longitudinally.

Glioma is the one of the most lethal forms of human cancer. The most effective glioma therapy to date-surgery followed by radiation treatment-offers ...

Minimal Erythema Dose (MED) Testing

Ultraviolet radiation (UV) therapy is sometimes used as a treatment for various common skin conditions, including psoriasis, acne, and eczema. The dosage of UV light is prescribed according to an individual's skin sensitivity. Thus, to establish the proper dosage of UV light to administer to a patient, the patient is sometimes screened to determine a minimal erythema dose (MED), which is the amount of UV radiation that will produce minimal erythema (sunburn or redness caused by engorgement of capillaries) of an individual's skin within a few hours following exposure. This article describes how to conduct minimal erythema dose (MED) testing. There is currently no easy way to determine an appropriate UV dose for clinical or research purposes without conducting formal MED testing, requiring observation hours after testing, or informal trial and error testing with the risks of under- or over-dosing. However, some alternative methods are discussed.

Minimal Erythema Dose MED Testing

This article describes how to conduct minimal erythema dose (MED) testing in order to determine the lowest dose of ultraviolet radiation that will cause erythema (burning) when administered to an individual.

Ultraviolet radiation (UV) therapy is  sometimes used as a treatment for various common skin conditions, including  psoriasis, acne, and eczema. The ...

Dual-phase Cone-beam Computed Tomography to See, Reach, and Treat Hepatocellular Carcinoma during Drug-eluting Beads Transarterial Chemo-embolization

The advent of cone-beam computed tomography (CBCT) in the angiography suite has been revolutionary in interventional radiology. CBCT offers 3 dimensional&#160;(3D) diagnostic imaging in the interventional suite and can enhance minimally-invasive therapy beyond the limitations of 2D angiography alone. The role of CBCT has been recognized in transarterial chemo-embolization (TACE) treatment of hepatocellular carcinoma (HCC). The recent introduction of a CBCT technique: dual-phase CBCT (DP-CBCT) improves intra-arterial HCC treatment with drug-eluting beads (DEB-TACE). DP-CBCT can be used to localize liver tumors with the diagnostic accuracy of multi-phasic multidetector computed tomography (M-MDCT) and contrast enhanced magnetic resonance imaging (CE-MRI) (See the tumor), to guide intra-arterially guidewire and microcatheter to the desired location for selective therapy (Reach the tumor), and to evaluate treatment success during the procedure (Treat the tumor). The purpose of this manuscript is to illustrate how DP-CBCT is used in DEB-TACE to see, reach, and treat HCC.

Dual-phase cone-beam computed tomography (DP-CBCT) is a useful intraprocedural imaging technique for transarterial chemo-embolization treatment with drug-eluting beads of hepatocellular carcinoma. DP-CBCT has been used to perform three major steps in oncologic interventional radiology: tumor localization (see), navigation and intraprocedural catheter guidance (reach), and intraprocedural evaluation of treatment success (treat).

The advent of cone-beam computed tomography (CBCT) in the angiography suite has been revolutionary in interventional radiology. CBCT offers 3 ...

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson&#39;s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.
Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson&#39;s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Controlling Parkinson&#039;s Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) is effective for Parkinson&#8217;s disease, improving symptoms and reducing power consumption compared to conventional deep brain stimulation (cDBS). In aDBS we track a local field potential biomarker (beta oscillatory amplitude) in real time and use this to control the timing of stimulation.

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time ...

Voluntary Breath-hold Technique for Reducing Heart Dose in Left Breast Radiotherapy

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these techniques, patients hold their breath while radiotherapy is delivered, pushing the heart down and away from the radiotherapy field. Despite clear dosimetric benefits, these techniques are not yet in widespread use. One reason for this is that commercially available solutions require specialist equipment, necessitating not only significant capital investment, but often also incurring ongoing costs such as a need for daily disposable mouthpieces. The voluntary breath-hold technique described here does not require any additional specialist equipment. All breath-holding techniques require a surrogate to monitor breath-hold consistency and whether breath-hold is maintained. Voluntary breath-hold uses the distance moved by the anterior and lateral reference marks (tattoos) away from the treatment room lasers in breath-hold to monitor consistency at CT-planning and treatment setup. Light fields are then used to monitor breath-hold consistency prior to and during radiotherapy delivery.

The current priority in breast cancer radiotherapy is to reduce cardiac doses without compromising target tissue coverage. The voluntary breath-hold technique described here is a simple, inexpensive solution to this problem and capable of being instituted widely without the need for specialized equipment.

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these ...

Non-fluoroscopic Catheter Tracking for Fluoroscopy Reduction in Interventional Electrophysiology

A technological platform (MediGuide) has been recently introduced for non-fluoroscopic catheter tracking. In several studies, we have demonstrated that the application of this non-fluoroscopic catheter visualization system (NFCV) reduces fluoroscopy time and dose by 90-95% in a variety of electrophysiology (EP) procedures. This can be of relevance not only to the patients, but also to the nurses and physicians working in the EP lab. Furthermore, in a subset of indications such as supraventricular tachycardias, NFCV enables a fully non-fluoroscopic procedure and allows the lab staff to work without wearing lead aprons. With this protocol, we demonstrate that even complex procedures such as ablations of atrial fibrillation, that are typically associated with fluoroscopy times of &#62;30 min in conventional settings, can safely be performed with a reduction of &#62;90% in fluoroscopy exposure by the additional use of NFCV.

Radiation exposure is an underestimated risk in complex ablation procedures. Here, we describe a protocol to significantly decrease fluoroscopy time and dosage for both the patient and the lab staff by using a novel non-fluoroscopic catheter visualization system.

A technological platform (MediGuide) has been recently introduced for non-fluoroscopic catheter tracking. In several studies, we have demonstrated that ...

Real-time X-ray Imaging of Lung Fluid Volumes in Neonatal Mouse Lung

At birth, the lung undergoes a profound phenotypic switch from secretion to absorption, which allows for adaptation to breathing independently. Promoting and sustaining this phenotype is critically important in normal alveolar growth and gas exchange throughout life. Several in vitro studies have characterized the role of key regulatory proteins, signaling molecules, and steroid hormones that can influence the rate of lung fluid clearance. However, in vivo examinations must be performed to evaluate whether these regulatory factors play important physiological roles in regulating perinatal lung liquid absorption. As such, the utilization of real time X-ray imaging to determine perinatal lung fluid clearance, or pulmonary edema, represents a technological advancement in the field. Herein, we explain and illustrate an approach to assess the rate of alveolar lung fluid clearance and alveolar flooding in C57BL/6 mice at post natal day 10 using X-ray imaging and analysis. Successful implementation of this protocol requires prior approval from institutional animal care and use committees (IACUC), an in vivo small animal X-ray imaging system, and compatible molecular imaging software.

We present a protocol to assess the rate of alveolar fluid clearance or pulmonary edema in neonatal mouse lung using X-ray imaging technology.

At birth, the lung undergoes a profound phenotypic switch from secretion to absorption, which allows for adaptation to breathing independently. Promoting ...

Two-Dimensional X-Ray Angiography to Examine Fine Vascular Structure Using a Silicone Rubber Injection Compound

Angiography is an essential tool for the study of vascular structures in various research fields. The aim of this study is to introduce a simple angiographic method for examining the fine vascular structure of unfixed, fresh tissue using a silicone rubber injection compound and soft tissue X-ray system. This study is especially focused on flap territories used in reconstructive surgery. This study employs angiography with a silicone rubber injection compound in various experimental conditions using Sprague-Dawley rats. First, 15 mL of MV compound and 15 mL of diluent is mixed. Then, 1.5 mL of the curing agent is prepared, and a 24G catheter is cannulated in the common carotid artery of the rat. A three-way stopcock is then connected to a catheter, and the radiopaque agent, after being mixed with the prepared curing agent, is injected immediately without spillage. Finally, as the agent solidifies, the specimen is harvested, and an angiographic image is obtained using a soft tissue X-ray system. This method indicates that high-quality angiography showing fine vascular structures can be easily and simply obtained within in a short period of time.

This study presents a simple two-dimensional angiographic method to examine fine vascular structures using a silicone rubber injection compound and soft tissue X-ray system.