Thursday, October 8, 2020

VERIFYING SIGNS OF COVID-19 STROKE THROUGH IMAGING

 By: Robert L. Bard, MD  and Dr. Pierre Kory, MD

ABSTRACT 
Early detection and prevention of arterial and venous disease is key to minimizing the effects of arterial obstruction & hemorrhage,  brain aneurysms, and strokes from venous thrombosis.  The association of trauma to PTSD is now followed by advanced Doppler ultrasound and functional MRI. This abnormal physiology may also manifest as arterial dissection, collagen disease, inflammatory arthritis, dermatitis, ocular disorders, GI disturbances, limb pain, aneurysms of the brain and aorta. Devastating strokes in the Covid-19 era occur in the younger age group and the Latin population is at higher risk.


INTRODUCTION 
Interest in arteritis was elevated with the study of Tayakasu’s disease in the 1970s when advances in contrast arteriography diagnosed diffuse vascular involvement causing strokes and aneurysms in multiple sites. While this arterial inflammation is more common in Asians, in the US, blacks are nearly three times more likely to have a stroke at age 45 than whites. The pediatric population seems to be at higher risk for this arteritis as evidenced by their unusual rate of Covid-19 affliction affecting the vasculature and called “MULTIPLE ACUTE INFLAMMATORY SYNDROME“. Birth control pills is a distinct cause of such disease in younger women while cancer, alcoholism and obesity raise the incidence at all ages.


We have learned over the last century that blockages of coronary arteries to the heart and carotid arteries to the brain are precipitated by inflammation of the inner walls of the vessel, called the “intima”

While thickening of the interior wall of vessels gradually occurs over time and is aggravated by diet, stress and hypertension (high blood pressure), the acutely disabling event is when there is an abrupt tear of the overlying plaque which ruptures debris which then forms a blood clot which blocks blood flow or the clot travels deeper into the brain and blocks blood flow. Similarly, abnormal heart rhythms such as “atrial fibrillation”, causes the pooling of blood in the heart which predisposes to clot formation and the clots can then travel into the brain causing a stroke. In Covid-19, the virus causing severe inflammation in the blood which then promotes clot formation which can travel through the vascular system and affect  almost every organ system in the human body, with the brain and lungs being the most affected.. An article in September NEUROLOGY reported by Medscape documented the incidence of large artery stroke as the presenting symptom of  COVId-19 was highest in men under the age of 50 years. 

HISTORY
A medical research team at Metropolitan Hospital in New York first noticed unusual neurologic symptoms in young and middle aged patients in the late 1960s. As a division of the NY Medical College system, they were fortunate to have an active interventional radiology department specializing in neuroimaging and arteriography. The observation of distortion and occlusion of arteries supplying the brain, kidneys, GI tract and lower limbs to various degrees from single to multiple locations was closely linked to the Japanese disorder known as Tayakasu’s arteritis at the time and recently renamed “arteritis.” A clinical finding of this arterial inflammation in the abdominal aorta was pain in the upper abdomen by the great vessels by palpation. Astute physicians were successfully treating this with commonly available “aspirin.”

However, the chronic and diffuse nature of arteritis often weakened the vessel wall producing aneurysmal dilation and rupture. Today we find sophisticated non-invasive or minimally invasive modalities to be the first line of interrogation of vasculitis.

COVID AND STROKE
COVID-19 was rapidly understood as a disease caused by severe and widespread inflammation and “hypercoagulability” (a tendency to spontaneously form clots in the blood vessels. Autopsies have revealed extensive small vessel strokes, with such strokes often occurring despite aggressive blood thinner treatment and regardless of the timing of the disease course, suggesting that it plays a role very early in the disease process. In one autopsy series, there was a widespread presence of small clots with acute stroke observed in over 25%. In a recent review of the incidence of stroke in COVID-19, almost 2% of all hospital patients suffered a stroke, which is 8x higher than in patients with influenza. More worrisome is that this is almost definitely a gross underestimate given the many likely missed strokes in patients who died on ventilators who were too ill to obtain imaging, the general restrictions on and lack of autopsies, and the well-recognized decrease in the number of patients with acute stroke symptoms seeking medical attention in the COVID-19 era.  Another worrisome finding from a recent study of COVID-19 cases found that 45.5% of patients reported neurologic symptoms [4]. This under-recognized epidemic of neurological symptoms and strokes in COVId-19 highlights the need for more intensive imaging and investigation to achieve not only earlier recognition and improved treatment of patients but in furthering understanding of COVID-19 effects on brain function.

DIAGNOSIS BY IMAGING
Blood flow abnormalities in the arterial system are best study by Doppler imaging like the weather Doppler showing tornadoes. Multiple options exist for blood flow analysis including:

- CAROTID SONOGRAM
- CAROTID DOPPLER
- EYE SONOGRAPHY
- TRANSORBITAL DOPPLER
- CONTRAST ENHANCED ULTRASOUND
- TRANSCRANIAL DOPPLER
- HYBRID IMAGING

- 3D/4D VESSEL DENSITY HISTOGRAM
- ENDOARTERIAL 3D DOPPLER
- RETINAL OCT
- SOFT TISSUE OCT
- REFLECTANCE CONFOCAL MICROSCOPY
- SMALL COIL MRI
- 7 TESLA MRI


CAROTID SONOGRAM:
While cerebrovascular disease is often diagnosed ex post facto after a catastrophic episode with MRI and CT, the non invasive Doppler analysis of the vascularity is generally checked with ultrasound for plaque and obstruction. A useful measure of the risk of coronary and cerebrovascular disorder is the carotid intimal thickness (CIMT). Standard depth of the inner wall thickness is a measure best obtained by high resolution sonograms since a reading over 0.9mm indicates increased risk. The newer sonogram units have depth resolution of 0.02mm making this a preferred non invasive option.

CAROTID DOPPLER: Flow abnormalities of turbulence and absence are commonly evaluated with this modality. Plaque forms more readily in aberrant flow patterns and high velocity regions accompanying narrowing.

EYE SONOGRAPHY: Sonofluoroscopy of the orbital soft tissues and eyes is performed in multiple scan planes with varying transducer configurations and frequencies. Power and color Doppler use angle 0 and PRF at 0.9 at optic nerve head. 3D imaging of optic nerve and carotid, central retinal arteries and superficial posterior ciliary arteries performed in erect position before and after verbal communication. Retinal arterial flow is measured. Optic nerve head bulging is checked as increased intracranial pressure may be demonstrable.

TRANSORBITAL DOPPLER: R/L ciliary arteries have normal Doppler flows of 10cm/s which is symmetric.

CONTRAST ENHANCED ULTRASOUND: Widely used European nonionic contrast injection allows imaging capillary size vessels and perfusion characteristics

TRANSCRANIAL DOPPLER: This measures the flow in the anterior, middle and posterior cerebral arteries as well as Circle of Willis.

3D/4D VESSEL DENSITY HISTOGRAM: Multiple image restoration and reconstruction shows retinal vessel density of 25% at the optic nerve head and adjacent region with quantitative accuracy.

ENDOARTERIAL 3D DOPPLER: Microcatheters inserted into the arterial or venous system provide measurement of wall thickness and presence of inflammatory vessels inside the intima.

RETINAL OCT: Subtraction techniques done with OCT optical coherence tomography may show changes in the caliber of the retinal vessels with verbal ideation.

SOFT TISSUE OCT: The depth of penetration may be extended to 2-3mm allowing for analysis of vascular changes in erythematous or erythropoor dermal areas. Thrombosis may be observed.

REFLECTANCE CONFOCAL MICROSCOPY: This microscopic analysis of the cells also quantifies microvascular pathology and is a potential modality for studying vasculitis.

SMALL COIL MRI: High resolution systems used for animal study and superficial organs can image the intra-arterial anatomy including dynamic contrast imaging on standard 1.5T and 3T units.

7 TESLA MRI: High field systems analyse signal abnormalites rapidly with high resolutions.

HYBRID IMAGING: Hybrid imaging refers to combining diagnostic modalities to assess disease and monitor therapy. 


TREATMENT OPTIONS
CEUS and nanoparticle delivery of dexamethasone may be used to reduce plaque inflammation and stroke occurrence. Intraarterial unstable plaque, most commonly found in the carotid artery, readily ruptures (acutely blocking flow) or dislodges causing distal embolism and arterial occlusion often in the brain, extremities and GI tract. While the composure of this plaque is mostly fibrin and lipid, it is the ulceration, bleeding and active inflammation that produces catastrophic outcomes. Neovascularization plays a central role in plaque initiation, progression and rupture. Quantifying these inflammatory microvessels is a surrogate marker of plaque instability and stroke risk. Histopathologic evidence shows plaque with high vessel density is more likely to rupture. [5]

SUMMARY
Covid-19 affliction of the arterial and venous systems with clot formation and vessel inflammation affect every organ system in the body. Arteritis of the small vessels involves the lungs, heart, brain, kidneys and liver predominantly which increases stroke risk in the absence of other contributing factors. Advanced ultrasound imaging offers early detection alerts and image guided therapeutics are now available. Anti inflammatory treatments, such as the MATH+ protocol used to treat Covid-19 pulmonary disease, might be useful in reducing intra-arterial inflammation and preventing plaque rupture.


REFERENCE

1. Hassani SN, Bard RL: Ultrasonic Diagnosis of Abdominal Aortic Aneurysms.

 J. Natl. Med. Assoc. 66:298-299, July 1974

2. Lande A, Bard RL: Arteriography of Pedunculated Splenic Cysts. Angiology 25:617-621, October 1974

3. Lande A, Bard RL, Rossi P: Takayasu's Arteritis: A World Entity. N.Y. State J. Med. 76:1477-1482, Sep 1976

4. Helbick Eur Radiol 30:5536-5538, 2020

5. Mao l  JAMA Neurol 2020 77:683-690

 

CONTRIBUTORS

ROBERT L. BARD, MD, PC, DABR, FASLMS
Advanced Imaging & Diagnostic Specialist
Dr. Bard received the 2020 nationally acclaimed Ellis Island Award for his lifetime achievement in advanced cancer diagnostic imaging. He co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- www.CancerScan.com) uses the latest in digital imaging technology and has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. Imaging solutions such as high-powered sonograms, Power Doppler Histogram, sonofluoroscopy, 3D/4D image reconstruction and the Power Doppler Histogram  are safe, noninvasive, and do not use ionizing radiation. 



PIERRE KORY, M.D., M.P.A.
Dr. Kory is Board Certified in Internal Medicine, Critical Care, and Pulmonary Medicine. He served as the Medical Director of the Trauma and Life Support Center at the University of Wisconsin where he was an Associate Professor and the Chief of the Critical Care Service. He is considered a pioneer and national/international expert in the field of Critical Care Ultrasound and is the senior editor of the widely read textbook “Point-of-Care Ultrasound” (winner of the President’s Choice Award for Medical Textbooks from the British Medical Association in 2015).  Most recently, Dr. Kory joined the emergency volunteer team during the early COVID-19 pandemic in NYC at Mount Sinai Beth Israel Medical Center. He is also a founding member of the Front Line COVID-19 Critical Working Group (flccc.net) composed of 5 critical care experts that devised the COVID-19 treatment protocol called MATH+. (www.covid19criticalcare.com/)

Thursday, October 1, 2020

What is HIFU? High Intensity Ultrasound for the Treatment of Cancer

INTRODUCTION TO HIFU

By: Dr. Robert L. Bard  |   Graciella Davi | Editorial Staff @ NY Cancer Resource Alliance

Medical science has taken significant leaps in the past three decades with the advent of a non-invasive approach to surgical investigation and treatment modalities.  This movement was greatly prompted by the need to reduce or eliminate the many significant risks and hidden dangers of cutting through the skin and vital organs.  Technologies such as the ULTRASOUND offers the medical community life-saving alternatives that ensures quantifiable results without the  potential dangers to the patient. (also see "No More Scalpel" and "Bye Bye Biopsies")

Pursuing the concept of safe, non-surgical alternatives, the principle of HIFU is based on controllable high energy sound waves, which leads to coagulation necrosis at the focal point. It can be applied for different indications: complete ablation of prostatic tissue is attempted in whole gland HIFU in the primary treatment of localized prostate cancer. [1] The first therapeutic trial of high intensity ultrasound beams was carried out in 1942. The Fry brothers are credited with the first application of HIFU for neurologic disorders in humans. Early attempts to generate HIFU lesions in the brain through the intact skull bone were unsuccessful. Jan 10, 2011 [2]



HIFU: THE NEXT WAVE OF NON-INVASIVE CANCER TREATMENT By: Dr. Robert L. Bard 

Prostate cancer, certainly the most common cancer among men, might be considered a two-headed hydra. On the one hand, some of these tumors, especially among African-Americans are aggressive, resulting in premature death. On the other hand, many of these tumors are slow growing and for a significant subset of patients, watchful waiting is recommended. But it is difficult to watch and wait when you believe that a cancer is growing within.

The quest for minimally invasive treatments of prostate tumors has been ongoing since the 1990’s. There have been advocates of focal freezing as well as heating of prostate tissue that results in the destruction of prostate cancers. Focal cancers may be targeted by high intensity focused ultrasound beams (High Intensity Focused Ultrasound or HIFU) and have been in clinical practice for 25 years. Developed simultaneously in the US (Sonoablate 500) and France (Ablatherm) the technique is favored by men wishing to avoid possible complications or side effects of surgery or radiation therapy. 

Treatment is usually performed under anesthesia. Energy is delivered to malignant tissue using in this instance, high frequency ultrasound waves that heats the tissue above 40 degrees Centigrade destroying the tissue.  Tissue temperature is closely monitored by sophisticated electronics to minimize adjacent tissue damage which can result in narrowing of the urethrae and obstruction of the flow of urine. Additionally, nerves involved in sexual performance may be inadvertently heated resulting in some degree of sexual dysfunction. 

A recent study reported in the Journal of Urology looked at 52 patients treated with this technique. The results are mixed. Patients included all had localized biopsy proven prostate cancers. The study defined treatment failure as recurrence on follow up biopsy at 20 months showing recurrent or higher grade tumor, metastatic spread systemic therapy or cancer specific mortality. 

  • There were 13 minor complications of which urinary retention was the most common.  There were no deaths and no cases of rectal injury.
  • Of the 60% of individuals undergoing repeat biopsy, 83% had no residual tumor

This study was limited in two significant ways. First, nearly a quarter of the patients underwent simultaneous “debulking” of prostate tissue by conventional surgical means in order to treat pre-existing difficulties with urination. Second, if biopsy is to be considered the outcome of importance, then 40% of the patients did not complete the study. It did not recognize that microscopic analysis of biopsies is limited by the posttreatment effect on the gland and the gold standard for pathology has been whole gland analysis after radical prostatectomy.


UCLA Health is among the world’s most comprehensive academic health systems, with a mission to provide state-of-the-art patient care, train top medical professionals and support pioneering research and discovery. It includes four hospitals on two campuses — Ronald Reagan UCLA Medical CenterUCLA Mattel Children’s Hospital and the Stewart and Lynda Resnick Neuropsychiatric Hospital at UCLA in the Westwood area of Los Angeles, and UCLA Health - Santa Monica Medical Center – and more than 200 medical practices throughout Southern California. UCLA Health also includes the David Geffen School of Medicine at UCLA.


VIEWPOINTS:

Treatment will be more effective on smaller volume glands and low grade cancer. As an imaging specialist, the problem with biopsies is that the cells under the microscope may look malignant but the tumor is clinically indolent or inactive. Biopsies are random and the area presumed to be a cancer may have active malignancy in one area, scarring in another, benign tissue adjacent or immune cells attacking the injured tissue.  Most post treatment biopsies are guided by blood vessel flow study with contrast MRI or 3D Doppler in the cancer site since PSA is not very reliable. The targeted area is the region of greatest arterial tumor arterial concentration.  [J Urol 2016]

Worldwide the aggression of a tumor is determined by the activity of the feeding blood vessels. Generally ablative treatments are deemed successful when there are no more arterial suppliers demonstrable by the various blood flow perfusion imaging technologies (Doppler ultrasound, CT dye, MRI contrast)  It is well known that there is a PSA rise in the presence of inflammation as well as recurrence which is non diagnostic. Over many years the cancer statistics observed that the re-occurrence of malignancy in 5 years falls between 10-30% regardless of the treatment delivered.


OTHER NON-INVASIVE CANCER SOLUTIONS

ADVANCEMENTS IN PROTON THERAPY
It is commonly observed that surgeons are increasingly using minimally invasive procedures. Whether it's robotic or video assisted surgeries, we can identify the pattern of new treatment protocols to result in higher quality of life and a reduction in toxicity. In doing so, it allows us, in some cases, to actually improve survival through those same methods of reducing toxicities for patients. According to Dr. Charles B. Simone II, Chief Medical Officer of the New York Proton Center, “We’re going to see more and more customized treatment; it's not a one size fits all approach to cancer. We are going to have individualized ways to deliver radiation therapy, individualized drugs or immune agents—and then, potentially more synergy between modalities such as radiation with systemic therapies.” (See article link)


CYBERKNIFE® AND THE ERA OF ETHICS IN ENGINEERING
Today's engineering and medical technology (from the late 1980s) show significant evidence of ethical standards and major consideration for patient response. Ethics in treatment engineering covers all angles considered about the innovation including: the way it is built, the materials applied, the engagement of the operator and the aftermath of the patient.. “Historically, radiation CAUSED cancer, but that's because you didn't have precision then. You were basically irradiating healthy tissue. That's what you want to avoid at all costs. So the more precise you can be, the better - and we (Accuray) pride ourselves on exquisite and unparalleled precision,” says Ms. Fleurent. (See article link)





About the Author:

DR. ROBERT L. BARDMD, PC, DABR, FASLMS 
For over 40 years, Dr. Bard is recognized internationally for his advanced clinical work in non-invasive cancer diagnostic imaging. His wide body of work is catalogued in countless medical texts and journal articles about the continued advancements in quantitative 3-D Ultrasound Doppler Imaging. In addition, he has been a major advocate for early detection in many high-risk professionals such as first responders, law enforcement and military personnel. Today,  Dr. Bard continues to respond to major health crises like the Coronavirus pandemic with his collaborative research work in chest ultrasound scanning of covid-related issues and the launch of his Medical Virtualization campaign -supporting "borderless medicine" and improved technical response to emergency medical calls.


GRACIELLA DAVI is a public health and safety advocate, an environmental researcher and a publisher for Prevention101, ImmunologyFirst.org, Awareness for a Cure and (fmr) EcoSmart News.  As an educator and writer, her career is dedicated to providing FACT-CHECKED NEWS in assignments concerning health, safety, science and environmental news.  This includes a wide list of studies in Cancer causing agents and pathogenic response and medical innovations.  



REFERENCES

1) High intensity focused ultrasound (HIFU) : Importance in the treatment of prostate cancer https://pubmed.ncbi.nlm.nih.gov/28439616/#:~:text=Results%3A%20The%20principle%20of%20HIFU,treatment%20of%20localized%20prostate%20cancer.

2) High intensity focused ultrasound in clinical tumor ablation - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095464/#:~:text=HIFU%20BACKGROUND-,History,unsuccessful%5B8%2C10%5D.

Sources: Prospective Evaluation of Focal High Intensity Focused Ultrasound for Localized Prostate Cancer Journal of Urology DOI: 10.1097/JU.0000000000001015



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