Impact of Ultrasound on Medical Imaging: 1967–2021

In 1967, a weekly feature for medical school seniors was the ‘bullpen’ in the Charity Hospital amphitheater. Students were assigned a patient and given 30 minutes to do a history and physical exam and then present their differential diagnosis and recommendations to an attending. Diagnosis was almost exclusively based on the history and physical examination. Laboratory studies were generally confined to basic electrolytes, a CBC, urinalysis, sputum stains, and a chest x-ray.

This prepared me well for internship and residency on the Osler Medical Service at Johns Hopkins Hospital. Interns were on call 24 hours a day for 6 days a week and usually spent 16 to 18 hours a day attending patients at the bedside.

On Osler, there were no computers and handwritten or typed paper records hung on a chart rack. The wards were not air-conditioned, and yellow curtains separated each of the 28 beds. There were no patient monitors, IV pumps, or respirators, and interns performed all of the basic lab work on their patients. Nursing care was excellent; the house staff and nurses worked as a team caring for the patients. Lack of technology was compensated for by close and direct interaction with the patients and their families, and the practice of medicine was extremely satisfying and filled with empathy and compassion.

The patient was the object of all of our attention. In the late 1960s, imaging was limited and played a relatively minor role in diagnosis and management. Defensive medicine was not a concern.

Following my internal medicine residency at Hopkins, I spent the next 3 years in the immunology branch of the National Cancer Institute in Bethesda. The research centered on the new field of bone marrow transplantation and treatment of graft vs. host disease.1 Whole-body radiation prepared candidates for transplantation and my experience in dealing with near-lethal doses of radiation led me to pursue a career in radiation oncology.

After completing a residency in general and therapeutic radiology in 1975, I joined the staff of the Ochsner Clinic in New Orleans, practicing a combination of radiation therapy and general radiography and fluoroscopy. Imaging was film-based, with studies hung on multipanel viewboxes for interpretation and a hot light for image processing. Cases were dictated directly to a transcriptionist in a cubicle next to the reading room and were typed and signed in real time. The daily workload included 40 to 50 barium studies along with numerous oral cholecystograms, intravenous urograms, and chest and bone radiographs. Specialized imaging consisted of polytomography, penumoencephalography, lymphangiography, and angiography. Evaluation of the aorta, runoff vessels, and carotid vessels was performed by direct puncture. Women’s imaging consisted of xeromammograms, hysterosalpingography, and pelvimetry. Image-guided intervention was nonexistent.

That year, ultrasound was in its early clinical development and I acquired a machine and placed it in the radiation therapy department and began scanning patients from the nearby emergency department. At that time there were no other sectional imaging modalities (CT was not yet available for clinical use.).

A large part of the challenge of ultrasound was learning anatomy in a completely new way. As a result, my groundwork in understanding sectional anatomy came from ultrasound. Ultrasound, unlike CT and MR, permitted imaging not only in standardized axial planes but allowed scan planes in virtually any orientation, requiring a very detailed knowledge of anatomy.

In 1976, upon the retirement of Dr. Seymour Ochsner, I became Chair of the department at Ochsner. This provided me with an opportunity to re-equip the department at a time that the entire field of imaging was undergoing immense change. With ultrasound, new findings were being reported regularly2, and the overall quality of ultrasound images often exceeded those of early body CT scans.

The development of Doppler ultrasound in the late 1970s further expanded the applications of ultrasound, although prior to the introduction of color Doppler, this was mainly of interest to vascular surgeons, and diagnosis was based on waveform analysis rather than imaging.

An important technological development at the end of the 1970s was real-time ultrasound, leading to the rapid development of new applications in obstetrical, abdominal, pediatric, and intraoperative imaging3,4.

Developments in computers in the early 1980s led me to an opportunity to participate in the development of exciting new technologies, including a breakthrough involving ultrasound and providing a method to image Doppler information. Working with a small company in Seattle and a large prototype device, we generated the first images of blood flow in the abdomen and peripheral vessels using color Doppler5,6. Color Doppler, by allowing Doppler information to be shown in an image rather than as a waveform, was important in getting radiologists interested in Doppler. Today, color Doppler is an integral part of the ultrasound examination.

A less successful application of ultrasound in the 1980s was in the evaluation of the breast. Early breast scanners produced quality images by scanning the breast, as the patient lay prone in a water tank. Unfortunately, breast ultrasound was promoted aggressively by many manufacturers and by the mid-1980s was discredited as a useful addition to mammography. By the mid-1990s, however, advances in breast ultrasound demonstrated an important role in the evaluation of breast masses, making ultrasound an indispensable part of breast imaging and leading to the BI-RADS breast imaging and reporting system for ultrasound7–9.

Ultrasound also has had a major impact in providing guidance for minimally invasive diagnostic procedures. Fine-needle biopsy of lesions of the liver, kidney, retroperitoneum, as well as peripheral lymph nodes and the thyroid, have become a standard part of the diagnostic workup.

A radiologist of 50 years ago would not recognize the field if he or she were to return today. In fewer than 50 years, the computer has changed the practice of medicine. More precise and early diagnosis are clear benefits of the technology of the 21st century, but are accompanied by the perils of over utilization prompted by defensive medicine with interests of the physician potentially overshadowing those of the patient.

Although the contribution of these advances has benefited countless patients, many of the rewards of the practice of medicine have been diminished. In looking back at my 50 years of practicing medicine, recalling my final grand rounds at Charity Hospital, I appreciate the diagnostic skills acquired through history and physical examination, as well as the relationship I had with my patients during my clinical years. To me, this represents the real definition of being a physician. In many cases, these simple tools were often as effective, and certainly more satisfying, than today’s tendency to view the patient as the result of an imaging test rather than a person.

Christopher R. B. Merritt, MD, is a Past President (1986–1988) of the American Institute of Ultrasound in Medicine (AIUM) where he led the development of the AIUM/NEMA/FDA Output Display Standard, and served as a founder of the Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL).

References

  1. Merritt CB, Mann DL, Rogentine GN Jr. Cytotoxic antibody for epithelial cells in human graft versus host disease. Nature 1971; 232:638.
  2. Merritt CRB. Ultrasound demonstration of portal vein thrombosis. Radiology 1979; 133:425–427.
  3. Merritt CRB, Coulon R, Connolly E. Intraoperative neurosurgical ultrasound: transdural and tranfontanelle applications. Radiology 1983; 148:513–517.
  4. Merritt CRB, Goldsmith JP, Sharp MJ. Sonographic detection of portal venous gas in infants with necrotizing enterocolitis. AJR 1984; 143:1059–1062.
  5. Merritt CRB. Doppler colour flow imaging. Nature 1987; Aug 20; 328:743–744.
  6. Merritt CRB. Doppler color flow imaging. J Clin Ultrasound 1987; 15:591–597.
  7. Mendelson EB, Berg WA, Merritt CRB. Towards a standardized breast ultrasound lexicon, BI-RADS: ultrasound. Semin Roentgenol 2001; 36:217–225.
  8. Taylor KWJ, Merritt C, Piccoli C, et al. Ultrasound as a complement to mammography and breast examination to characterize breast masses. Ultrasound Med Biol 2002; 28:19–26.
  9. Berg WA, Blume JD, Cormack JB, et al. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA 2008; 299(18):2151–2163.

Ultrasound Can Catch What NIPT Misses

A few months ago a young couple, Michele and Dan, came to my office for a mid-trimester fetal anatomic survey at 21 weeks’ gestation. They were excited to see their fetus in 3D-4D ultrasound, and were wowed by the 3D image of their baby’s face. During the scan the couple related that they were sure their baby was OK “because the blood test came back negative,” and had decided to forego first trimester screening, despite their OB strongly recommending it.

unnamedThe blood tests, nuchal translucency measurement, and other sonographic parameters evaluated in first trimester screening are considered together to provide a risk profile for fetal chromosomal anomaly, particularly the risk of Down syndrome. If there is an increased risk, the parents may be advised to undergo invasive testing, such as chorionic villus sampling (CVS) or amniocentesis. In addition, first trimester screening can raise warning flags for structural anatomic malformations in the fetus, as well as other problems for the pregnancy. If first trimester screening includes a full fetal anatomic survey, it can spot about 40% of fetal malformations at a very early stage.

While I was reassured that Michele and Dan’s results on noninvasive prenatal testing (NIPT) meant the risk of their baby having Down syndrome and certain other aneuploidies was extremely low, I explained that structural malformations were still a much more common concern than chromosomal anomalies, and that a negative NIPT result did not rule out other conditions. Michele protested, “On the Internet it said that the blood test rules out Down syndrome 100%, that we didn’t have to worry.”

“The screening tests only give you a risk profile,” Dan insisted, “they don’t tell you if the baby is really affected. So we thought the blood test was the way to go.”

“I don’t want to have an amnio,” Michele continued, “I had a miscarriage in my last pregnancy,” she continued, as I proceeded to the echocardiography portion of the examination.

“Your baby appears to have a heart defect,” I said, as gently as I could, and began to explain the nature of transposition of the great arteries (TGA).

NIPT is the name applied to new techniques that use a sample of a pregnant woman’s blood to examine her fetus’s chromosomes. As early as 10 weeks of pregnancy there is sufficient fetal genetic material, called cell-free DNA, found in the maternal serum to allow analysis. A negative result from NIPT is a very good test to rule out Down syndrome in the fetus: it is highly specific, meaning that in almost all cases, a negative result is truly negative. NIPT is also highly sensitive, which means that in almost all cases, a positive result is truly positive. However, because there is a chance (however small) of a false positive (a healthy fetus may have a result showing him/her to have Down syndrome), a positive test result always needs to be confirmed with invasive testing, such as CVS or amniocentesis, before any decisions are made regarding the further management of the pregnancy. NIPT has also been found useful in identifying fetuses with other chromosomal anomalies and certain other genetic conditions. NIPT can also be used to determine the fetal sex.

However, while NIPT does a very good job at what it is designed for: looking at fetal chromosomal complement in specific conditions, it does not examine all the fetal chromosomes, nor does it look at the anatomy of the fetus. Fetal anatomy is examined in detail by ultrasound scanning. There is some debate among practitioners regarding the optimal week of pregnancy when full early fetal anatomy scanning should be performed. Some practitioners prefer performing the scan at the time of nuchal translucency screening, 11-13 weeks, while others prefer 14-16 weeks, when the fetal organs are more developed. The important point to remember: a fetus with a normal (negative) NIPT result can have an anatomic structural malformation. It has been shown that while fetuses with malformations may be at increased risk of chromosomal anomaly, the majority have healthy chromosomes. The diagnosis of a malformation by ultrasound should prompt invasive testing such as CVS or amniocentesis. In some centers, more detailed investigation by chromosomal microarray analysis (CMA), which may discover subtle anomalies, will also be ordered. CMA detects duplicated or deleted chromosomal segments and translocations—rearrangements of chromosomal structure, which may not be evident on traditional karyotyping.

NIPT is a very reliable test. But patients may have a false sense of security regarding their baby’s well-being. A negative NIPT result cannot rule out anatomic structural malformations in the fetus, nor does it rule out all chromosomal anomalies. There is ongoing debate surrounding the integration of NIPT into existing screening programs.

I continued to follow Michele and Dan in the weeks and months that followed. They were, of course, shocked and dismayed by their diagnosis. With Michele at 21 weeks, we immediately arranged multidisciplinary consultation with the cardiologists, who explained the procedures the baby would have to undergo, and how Michele’s plans for the birth would have to change. Prenatal diagnosis of TGA can improve the baby’s surgical outcome, and with prompt intervention, prognosis is excellent. They met with a genetic counselor, and despite Michele’s fears, underwent amniocentesis. CMA is performed in all such cases in our center. Testing ruled out genetic syndromes that we suspected based on the anatomic malformation, none of which could have been diagnosed by NIPT.

With comprehensive information in hand about their baby’s prognosis and the options open to them, Michele and Dan decided to continue the pregnancy, despite the difficult road they knew was ahead. They made arrangements for delivery in the tertiary care center where the baby would undergo surgery, so she would not have to be transferred from their community hospital and would be under constant surveillance. “I fell in love when I first saw the baby’s face in 3D,” she told me. “Whatever comes, we’ll handle it together.”

How do you think NIPT should be integrated into prenatal care? How do you advise your patients who ask about NIPT? Have you encountered patients with negative NIPT results whose fetus has a structural anomaly? Have you encountered patients with false negative or false positive NIPT? Comment below or let us know on Twitter: @AIUMultrasound.

Simcha Yagel, MD, is Head of the Division of Obstetrics and Gynecology Hadassah-Hebrew University Medical Centers, Jerusalem, Israel, and Head of the Center for Obstetric and Gynecological Ultrasound at the Hadassah-Hebrew University Medical Centers, Mt. Scopus, Jerusalem. He served as moderator for a panel discussion, “Noninvasive Prenatal Testing and Fetal Sonographic Screening,” that appeared in the March 2015 issue of the Journal of Ultrasound in Medicine.