SMARTER SAFETY PROTOCOL: IMAGE GUIDANCE IN THE HAIR RESTORATION PROCESS (part 2)

By:  Robert L. Bard, MD  / Edited by Lennard M. Gettz, Ed.D

From the standpoint of studying hair loss or androgenetic alopecia with non-invasive imaging, there appears a sensible solution to support both the management and research in a growing number of pharmaceutical and cosmetic treatments of this condition. The sonographic pre-depiction of the presence of remaining hair follicles in the dermis within epidermal dysfunction may suggest the optimal type of medical treatment (or surgical treatment). If we start with a basic premise of an area of the scalp with no hair follicles at all, current data may suggest that surgical or transplant treatment is the only option available. 

The diagnostic use of ultrasound or high resolution sonography for hair restoration procedures has been validated with electron microscopy in various key studies. Imaging innovations allow dermatologists and hair transplant specialists to identify follicles in their biologically active present condition.  Imaging advancements help to define follicles as either dormant/inactive, intermediary or active & healthy growing. Follicles in that inactive or dormant stage may suggest a decrease in follicular health, usually suggesting a delay surgical procedures and instead application of more topical or interventional treatment options into that area to boost the production of  scalp health and cellular regeneration.   In the case of normal & healthy hair; this is ideal to proceed with ultrasound guided transplant treatment. 

LAND MINES vs. IMAGE GUIDANCE
Hair transplants are considered minimally invasive procedures which often includes bleeding (due to its engagement with large blood vessels or aberrant arteries).  Because of this, potential risks may include tapping into unsuspected skin conditions like cancers nearby or underneath- often identified with the use of clinical imaging.  The term “scan and treat” is a research term that may also apply to clinical procedures.  In the case of IMAGE GUIDANCE, the inclusion of real-time ultrasound monitoring adds a significant layer of safety and added confidence in the technician’s role-- forging a more expedient treatment pace from potential surprises. 

During the implant process, there may exist certain LAND MINES like a subcutaneous tumor or a cluster of dilated vessels called a hemangioma that can bleed profusely. Occasionally there may also exist nerves that are traversing the base of the neck or shoulders that may accidentally be damaged in a postoperative situation. Since the micro vessels in the scalp bleed profusely, the formation of a blood clot or hematoma or inflammatory process can also be imaged. 

Today, we have the availability to use adjunct ultrasound features such as elastography, which shows scarring in the skin. In other words, scar tissue is hard and it may be more difficult to put a probe through heavily scarred tissue. Oftentimes areas that scar have micro or macro calcification – aptly called “an iceberg” of calcium or a bone underneath the area where the technician may be injecting or inserting stillets.  

Additionally, inflammatory disorders like skin cancers may reside under the scalp.  Use of a thermogram is also available to detect subdermal anomalies.  Finding a mass or a fluid collection is of concern. Fluid is avascular (no blood vessels) which means no heat. A big fluid spot will show up dark on our imaging with low temperature. Inflammation will appear as a brighter hot spot because it's full of inflammatory vessels. This procedure is used internationally to locate areas of wound healing. When a wound is healing correctly, there's very low temperature, what we might consider normal healing temperature. When an area is inflamed or is infected, the temperature in that given area is elevated and the thermogram represents this temperature increase as a bright spot correlating with the degree of inflammation. 

SCANNING PROCESS & PATHOLOGY
Once we have the top half of the skin (the dermis) covered optically or photographically, we may then apply high resolution ultrasound which starts from the epidermis and goes down to hit the bone. Instead of 200 micron depth, you have a hundred times greater penetration, around 2-20 centimeters of depth depending on the ultrasound transducer (or probe). The ultrasound is adjustable for targeting the exact site, depth wise. 

Today’s ultrasound probe designs are actually quite ideal for hair transplant process. There are a variety of probes (curve, flat, square, linear etc) that are designed for a wide range of unique applications.  Similar to ultrasound guided biopsies, integrating an ultrasound probe with an active transplant needle can call for PRO GUIDES where you can attach the device either to inject or to extract to the guide more accurately.  Having a live subdermal monitor available to you allows for an added level of safety as far as what NOT to target. If there's a nerve that you're about to hit or a large vein, or (hopefully not) a larger sized artery, you can avoid it as you're doing it.  So forewarned is forearmed in this case.

Diagnostically speaking, this imaging application can be used to uncover problems that cause the hair loss before it actually happens.  There are many cases where someone with a full head of hair can have inflamed follicles. You cannot see this with the naked eye even with magnification tools - but is easily identified with  ultrasound imaging in the mid part of the dermis and lower part of the dermis (where the follicles arise from).  This inflammation offers a prediction of upcoming hair loss if unmitigated.  It is from this imaging test that we are able to caution the patient about an underlying disorder. Upon further subclinical inquiry and investigation, we find such disorders to stem from hereditary baldness due to (possible) inflammatory skin disease such as rosacea or psoriasis.

Additionally, autoimmune diseases such as lupus and sometimes certain cancers cannot be seen from the skin- even though they may manifest eventually in hair loss.  Early indicators can be itching or redness, which in itself is a cause of scalp loss and great distraction to everyday normal functioning. Further investigation of this inflammation through clinical imaging may easily show the disease, how deep the inflammatory disease is- and then how aggressive it is.  

Recognizing the condition shows that abnormal skin appears white and inflamed- whereby normal dermis is dark.  Appearance of a whitish layer to a grayer and sometimes a darker level identifies the degree of inflammation. Then, we also look at the blood flow (which the 3D Doppler function provides) whereby the more inflammatory blood flow in the area, the more aggressive the disease may be.  This is the activity visible BELOW the skin. It may show up as a little redness on top, but the “real drama” occurs below the skin, which is why it's often missed clinically.  For this reason alone, use of clinical imaging such as ultrasound technology and other optical technologies are extremely important to see what is missed by the naked eye.

REFERENCES: 1) Usefulness of high-frequency ultrasonography in the assessment of alopecia areata – comparison of ultrasound images with trichoscopic images- https://pmc.ncbi.nlm.nih.gov/articles/PMC8953880/ (2) Innovative ultrasound scans to reduce hair follicle transection during follicular unit extraction for the hair transplantation- https://www.wcd2019milan-dl.org/abstract-book/documents/invited-speakers-abstracts/09-dermatological-surgery/innovative-ultrasound-scans-to-reduce-96.pdf   (3) Innovative Strategies for Hair Regrowth and Skin Visualization- https://pmc.ncbi.nlm.nih.gov/articles/PMC10141228/  (4) Images in Scalp Ultrasound Before and After Hair Transplant in Frontal Fibrosing Alopecia-  https://pubmed.ncbi.nlm.nih.gov/31725066/  (5) Transcutaneous application of ultrasound enhances the effects of finasteride in a murine model of androgenic alopecia  https://pmc.ncbi.nlm.nih.gov/articles/PMC8942741/

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WOMEN'S HAIR LOSS EXPLORED - FROM THE GENETIC RESEARCHER'S JOURNAL  By: Roberta Kline, MD

One of the most common causes of hair loss is ANDROGENIC ALOPECIA. This is related to androgen receptors called dihydrotestosterone.  We know that this is passed down through families. There is a significant hereditary component, but as of now, I have not yet found  a good discussion on what we know about the hereditary pattern in terms of what genes are linked to hair loss.

SNPs (pronounced "snip") = Single Nucleotide Polymorphism make up our genomic blueprint, and is a variation in a DNA sequence among individuals.  I don't believe hair loss is epigenetic; I believe it's most likely due to SNPs but it doesn't appear to always relate to the levels of androgens.  So this path of logic may not necessarily involve the metabolism, per se.  

As androgens are converted, testosterone gets converted into dihydrotestosterone (DHT), which is what binds to the hair follicle. Then testosterone gets metabolized into estrogen, and I learned more recently that there is actually a pathway where estrogen gets metabolized back into testosterone. From here, one could conclude that there are SNPs on androgen receptors involved.

When we look at women who have polycystic ovarian syndrome (which is not one disease), it's a spectrum, but they tend to have hormonal imbalances, insulin resistance and issues with excess androgens and imbalances between the estrogen and the androgens. Furthermore, they tend to have androgenic hair loss much earlier-  starting around twenties and thirties. So we know that these cases are significantly related to hormones. We know the hair loss is related to insulin and other things but this is part of my research about autoimmune diseases.

Autoimmune diseases tend to have some element of a hereditary pattern in terms of their predisposition. We know that polymorphisms and various genes related to the immune system and immune response, not only can they be inherited but they are linked to autoimmune diseases.  Understanding the genetics and the genomics of various types of hair loss can potentially build a knowledge base where we can see who might be predisposed and in those people, give them the foresight to intervene and potentially modify that predisposition.  This is part of a proactive approach to identifying early signs of hair loss, which often go missed.

Nobody will dispute that stress and certain toxins can cause hair loss. Observing one's predispositions may identify teltale clues supporting hair loss as a potential reaction to these jars to the system-- and there's even less research about this scenario on women.

In the case of Diane Pinson's early surprise hair loss (where she went completely bald in three days), logic dictates that such a dramatic symptom can only come from some type of TRAUMA.  As rare as this may seem, this is not It is not a gradual interruption of the hair follicle nore is it a gradual interruption or inflammation causing such a catastrophic loss of the hair. It's not a typical process that we know about -- this loss affects the hair follicle itself. The fact that her hair was able to grow back tells me that her hair follicles were okay- it was just that hormonally (along the way) they all got the signal to shed the hair at the same time.

Hormones are the body's communicators. When we talk about hormones, we think of the sex hormones. Most often, we first recognize estrogen, testosterone and the progesterone-- the metabolites. These are affected by other hormones such as insulin, cortisol and melatonin. These are all hormones and they are part of an intricate dance that coordinates communication among all sorts of different cellular processes and systems from the genes that run them. Unfortunately, we often get focused on one set of hormones, neglecting everything else.

HAIR REGEN CONCEPTS
The idea that topical hormones, estrogen and progesterone applied to the scalp can be effective in helping to grow or regrow hair. Theoretically, this makes sense if you understand how the hormones are affecting the hair follicles.  Certainly endogenous hormones, those that people take in terms of hormone replacement are linked to hair. We know that loss of estrogen leads to loss of hair throughout a woman's life cycle. So if somebody is adding testosterone locally to the hair follicle, and it's being absorbed in stimulating the hair follicle, it stands to reason that this can stimulate the growth phase of hair.

Inflamed Hair Follicle

ON IMAGING
I find the idea of using ultrasound to get a different perspective on the health of the scalp, the follicles and the related blood supply is a huge untapped area. The current standard is a topographical visual inspection (with a dermatoscope or a magnifier). Rarely does somebody get a biopsy of the scalp to identify its pathology, but Dr. Bard's use of the 3D Doppler ultrasound provides so much quantifiable information on the state of health of the skin that can potentially make the correct diagnosis faster and  can also provide much faster feedback on treatment efficacy. One of the challenges with many of the hair regenerative treatments is that they take a long time to show effect. You need repeated applications for months before you know whether it's actually working (or not).  Regular ultrasound monitoring with these treatments should actually provide a better indicator as to their effectiveness and when to expect those changes to occur.