Scanning Devices for Medical Applications – Part I

This is the essay commended by judges from Newnham College, Cambridge. I am delighted to share with you this work that took me almost a month to write and far longer to research. I loved the experience of writing this essay and immersing myself in this fascinating topic.

However, it is important to note that, since this was a 2500 word academic essay, it does make for heavier reading than my previous articles written specifically for this blog.

So brew some tea, find a comfortable reading nook, and settle in for this comprehensive exploration of the field of medical scanning from its origins over a century ago to its potential for the coming decades.

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PART I : ORIGINS AND X-RAYS

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The disciplines of engineering and medicine have long been intertwined, with physics concepts supporting the development of diagnostic tools and clinical demands fuelling exciting innovations in engineering.

Scanning devices for medical applications, all of which consist of an emitter and sensor, lie at the very heart of the intersection of these disciplines. Since its inception, over a century ago, this technology has been constantly evolving with new developments.

Origins
In a darkened laboratory in Würzburg, Germany (1895), an eerie glow emanating from a screen behind his cathode ray tube propelled Wilhelm Röntgen to discover invisible rays. These rays were capable of not only penetrating the heavy black paper insulating the Crookes tube but even Röntgen’s own skin. Astonished by his discovery of “a new kind of ray”, Röntgen began to experiment with the penetrating abilities of the x-ray to produce one of the first radiographs: his wife’s hand adorned with her engagement ring.

Shocked by the sight of the internal structures of her own hand, she reportedly gasped, “I have seen my death”. Despite such a macabre initial critique, x-rays captivated the world’s attention and optimism for their applications; Röntgen’s moment of serendipity gave rise to the ceaselessly evolving field of medical imaging.

X-Ray Modality Technology
X-rays are passed through the patient and are absorbed, to varying degrees, by different tissues in their body. In indirect flat-panel detection, unabsorbed x-ray photons are transmitted through the body and strike caesium iodide crystals in the first layer of the detector. The crystals scintillate when excited by radiation – emitting flashes of visible light proportional to the energy of the x-ray photons. Amorphous silicon photodiodes in the detector’s second layer transform light into electrical charges to produce digital images.

X-Rays and Cancer 
X-rays play an essential role in mammography; pre-cancerous breast tissue contains clusters of microcalcifications (minor calcium hydroxyapatite deposits) which act as major indicators of accelerated cell division. Microcalcifications can go undetected in biopsies. However, in x-ray scans, these deposits are clearly revealed as bright white specks due to their very high x-ray absorption – enabling early detection.

CT Scan
The humble x-ray also forms the basis of the revolutionary multisection CT scanner (a scanning device introduced in 1992 that aims a narrow beam of x-rays at the patient in a complete spectrum of angles); this device outputs multitudes of cross-sectional ‘slices’ (tomographic images) which can be digitally ‘stacked’ to produce three-dimensional models. The technique improves both diagnostic accuracy and spatial resolution in the Z axis due to the creation of thinner tomographic slices. This also reduces the risk of partial volume artefact formation (imaging errors which occur when tissues with varying thickness and radiation absorption are in close proximity).

EOS Scan
The latest x-ray modality technology addresses a major drawback of CT scanning: its significant radiation exposure. The EOS scanner, developed in 2007, is a vertical scanner consisting of two pairs of perpendicular radiation sources and detectors. This allows for precise 3D reconstruction as well as imaging of the skeletal system in its natural weight-bearing posture. This innovation helps clinicians identify and diagnose subtler issues which are only apparent in the patient’s skeletal system in the context of its typical load-bearing alignment (as opposed to its relaxed alignment when the patient is lying down in a CT scanner).

The implementation of revolutionary particle physics technology allows high-resolution (254 μm) radiographs to be taken with significantly less radiation exposure than CT scanners. The EOS scanner uses a proportional multiwire chamber (first developed by the Nobel Prize winner Georges Charpak) which enables extremely sensitive detection of even single x-ray photons – allowing a significant reduction in x-ray exposure without compromising the resolution.

This unique aspect makes it particularly suited for monitoring scoliosis in adolescents. Since scoliosis is eight times more prevalent and more severe in females than in males, adolescent girls are typically exposed to excessive radiation from the multiple CT scans (up to 5 per year) necessary to assess the progression of this condition. High level of radiation exposure, especially during a critical phase of rapid growth, increases the risk of developing cancer; growing breast tissue is highly sensitive to the carcinogenic effects of ionising radiation which cause a 69% increase in breast cancer incidence.

The EOS scanner, with its significantly lower radiation exposure, is proving to be vital in limiting the risk of cancers whilst safely monitoring scoliosis.

 

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The figures quoted in this essay have been meticulously researched and documented. Below is the bibliography for this section of my essay:

“History of Radiography.” NDT Resource Centre, National Science Foundation,
https://www.ndeed.org/EducationResources/CommunityCollege/Radiography/Introduction/history.htm [Last Accessed: 28 Jan 2019]

“X-Ray.” Wikipedia, Wikimedia Foundation Inc., https://en.wikipedia.org/wiki/X-ray [LastAccessed: 28 Jan 2019]

Cruz, Robert. “Digital radiography, image archiving and image display: Practical tips.” Canadian Veterinary Journal, 49.11 (2008): 1122-1123. PMC. Web. [Last Accessed: 04 Mar 2019]

Wang, Zhentian, et al. “Non-invasive classification of microcalcifications with phase-contrast X-ray mammography.” Nature Communications 5 (2014). Nature. Web. [Last Accessed: 01 Mar 2019]

Rydberg, Jonas et al. “Multisection CT: Scanning Techniques and Clinical Applications.” RadioGraphics 20.6 (2000): 1787-1806. RSNA. Web. [Last Accessed: 30 Jan 2019]

Bell, Daniel, and Vikas Garg et al. “Partial volume averaging (CT artifact)” Radiopedia, Radiopedia, https://radiopaedia.org/articles/partial-volume-averaging-ct artifact-1?lang=gb [Last Accessed: 30 Jan 2019]

Illés, Tamás, and Szabolcs Somoskeöy. “The EOS (TM) imaging system and its uses
in daily orthopaedic practice.” International Orthopaedics 36.7 (2012): 1325-1331.
ResearchGate. Web. [Last Accessed: 31 Jan 2019]

“Information and Support.” NSF, National Scoliosis Foundation,
https://www.scoliosis.org/info.php [Last Accessed: 02 Feb 2019]

Morin-Doody, Michele et al. “Breast cancer mortality after diagnostic radiography: findings from the U.S. Scoliosis Cohort Study.” Spine 25.16 (2000): 2052-2063. NCBI. Web. [Last Accessed: 02 Feb 2019]

Image Credits:

Röntgen, Wilhelm. “Hand mit Ringen (Hand with Rings).” Wikipedia, Wikimedia
Foundation Inc., 22 December 1895.

Hendriks, Eva, et al. “Regression of Breast Artery Calcification.” Cardiovascular
Imaging, Journal of the American College of Cardiology, August 2015.
http://imaging.onlinejacc.org/content/8/8/984/F1

EOS Imaging, Paris, France. A reconstructed 3D model of the full vertebrae of a
scoliosis patient based on an EOS TM 2D examination. Reproduced by Illés, Tamás in
International Orthopaedics 36.7 (2012): 1325-1331. Web. https://www.researchgate.net/figure/Full-body-surface-reconstructed-3D-model-based-on-an-EOS-TM-2D-examination_fig3_221867288

 

I was just informed that the essay I wrote for the Newnham Engineering Essay Prize was commended – I am absolutely ecstatic!

I will post my essay on scanning devices for medical applications soon…

Bluebell: Hyacinthoides non-scripta

[This post features my original artwork and botanical sketches]

I truly believe that revising for my upcoming exams and developing my understanding of the sciences is an enjoyable process, but when gentle dawn sunlight illuminates the vibrant azure bundles of flowers peppered throughout our garden, it takes the strength of every fibre in my being to not abandon my textbooks and immerse myself in the carpet of wild bluebells.

In two months, I’ll have sat all my AS exams and will finally be free to laze around in the grass with my cat and lie among the sea of indigo petals. Until then, I look to the shimmering haze of the bluebells as an oasis just fingertips away.

Recently, I rewarded my revision efforts by pressing an inflorescence and uncovering the chemistry behind their beautiful blue pigment*. The rich colour of the petals is not caused by a single true blue pigment but rather by the red pigment anthocyanin. The basic structure of the anthocyanin delphinidin is modified with pH shifts and prosthtic groups.

Delphinidin is pH sensitive and turns red in acidic environments. A high pH must be maintained to ensure the molecular pigment is blue. Delphinidin is also malonated; two glucosyl groups, a malonyl group, and a coumaryl group are bonded to the pigment structure. 

 

 

 

 

 

The resulting compound, malonylawobanin, is responsible for the brilliant deep blue petals that don’t even fade after weeks of pressing. 

I also consulted my copy of The Complete Herbal out of interest in the medicinal properties of this plant. Nicholas Culpeper was surprisingly brief in his writings of bluebells; he only refers to its somewhat styptic (blood clotting) qualities. From further research, I learnt that the bluebell’s intensely toxic nature has, understandably, limited its potential for therapeutic applications.

One of the major toxic compounds present in bluebells are polyhydroxylated pyrrolidines (such as nectrisine) which are found in the viscous sap that seeps out of the plant’s nodding stems. These compounds are analogues of sugar but are actually potent glucosidase inhibitors. Due to its many -OH groups, the mammalian body mistakes nectrisine as a sugar and processes it as such – inadvertantly allowing the molecule to interfere with respiration.

In addition to this, polyhydroxylated pyrrolizidines, which have a similar chemical action to nectrisine, are toxic alkaloids that have been proven to poison livestock that have the misfortune of ingesting bluebells. Despite this, these compounds are now being considered for use in cancer therapeutics.

Most fascinatingly, bluebells contain a type of cardiac glycoside, Scillaren A, which can rapidly increase the output force of the heart. Heart cells, myocytes, contain protein pumps embedded in their cell membranes which actively transport sodium ions out of the cell to create an essential electrochemical gradient. In the heart, there is also a sodium – calcium ion exchanger which maintains the ion homeostasis. 

Cardiac glycosides, such as Scillaren A found in bluebells, inhibit the movement of sodium ions out of the cell by effectively disabling the ion pumps. This increases the concentration of sodium ions inside the myocytes which, in turn, increases the calcium ion concentration as sodium ions inside the cell are exchanged for calcium ions.

In myocytes, the accumulation of calcium increases the power with which the cells can contract (contractility) – increasing cardiac muscle contraction which can be crucial in controlling the heart rate in cases of arrhythmia and even chemically restarting the heart in atrial fibrillation.

The cardiac action of Scillaren A is stronger than that of the commonly used digoxin, which is derived from foxglove, and is ideal for situations in which digoxin alone is insufficient or the patient has a digitalis intolerance. Additionally, if an improper dosage is administered, Scillaren A is poisonous but, unlike many other cardiac glucosides, is non-lethal as it is poorly absorbed into the gut. The compound also has a very high therapeutic index as it is rapidly eliminated from the body. All of these qualities make bluebells a fundamentally desirable pharmaceutical source, however, since native bluebells are an endangered and protected species, bluebells cannot be harvested to produce medication.

Conservation efforts are essential to protect and preserve this fragile, flowering species so that we may be able to enjoy their magnificent appearance and benefit from their therapeutic value in the coming decades.

 

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* White bluebells which lack pigmentation also exist albeit they are somewhat rare with only 1 in every 1000 native bluebells being white. Below is a pressed white bluebell I came across in Margate. 

Dandelion: Taraxacum Officinale

[This posts features my original botanical sketches]

For me, the most marvellous manifestations of spring are the bright dandelions emerging from previously barren, frost-glazed soil – bringing promises of brighter days to come.  The humble dandelion is so often maligned as a weed, however these perennial plants have a rich therapeutic history.

Nearly half a millennium ago, Nicolas Culpeper, a prominent herbalist of the early 1600s, noted that the dandelion has “an opening and cleansing quality” and remarked upon its efficacy at treating liver ailments (including cirrhosis) as well as diseases of the spleen and gall-bladder. Many of Culpeper’s contemporaries, and indeed modern herbalists, also acknowledge the powerful diuretic properties of dandelion leaves and root.

Dandelions have even proven valuable in cutting-edge pharmaceuticals. Researchers from the Department of Chemistry and Biochemistry at the University of Windsor, Canada,  have found that dandelion root extract can efficiently kill certain types of aggressive leukaemia cells. This extract can induce apoptosis (programmed cell death) and autophagy (wherein the cancer cell breaks down its own organelles), and even disrupt mitochondrial membranes. The lack of toxins and alkaloids in the plant, combined with the extract’s selectivity for leukaemia cells, makes the dandelion a particularly promising candidate for safe chemotherapy applications.

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Ovadje, P., Hamm, C., & Pandey, S. (2012). Efficient induction of extrinsic cell death by dandelion root extract in human chronic myelomonocytic leukemia (CMML) cells. PloS one, 7(2), e30604. doi:10.1371/journal.pone.0030604

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281857/