Breast imaging: newer developments

 Mammography is a medical imaging study that uses low dose x-rays to examine the human breast.  It can detect tumors before they are felt on physical examinationand can find microcalcifications that may indicate breast cancer.  Recently digital imaging has replaced film/screen mammography as it provides better image quality and allows easier storage and image sharing. Three dimensional mammography known as tomosynthesis is a newer mamographic technique which is useful in women with dense breast parenchyma.  Multiple randomized studies have demonstrated decreases in mortality from breast cancer by approximately 30% when screening mammograms are performed annually in women whose age is between 40 to 70. 

In 1990, Jackson in a Radiology article suggested ultrasound as a valuable tool in breast imaging especially when a mass is felt clinically or detected on mammography. Ultrasound helps in differentiating between solid masses that can be cancerous and fluid filled cysts that are benign.  In cases when a cancer is suspected ultrasound is used to guide needle biopsies and other therapeutic procedures such as breast cancer ablation. While useful, ultrasound is not a replacement for mammography.  For women with dense breasts when combined with mammography and clinical examination they provide a comprehensive evaluation.

In 1976, Frank, Ferris et al in a NEJM article described the technique of needle localization that allows placement of a wire with its tip adjacent to the lesion.  The technique ensures tat the surgeon can remove the suspicious finding with minimal tissue removal.  Wire localization can be performed either under mammographic or ultrasound guidance.

Magnetic resonance imaging (MRI) is using a magnetic field and radio waves to create detailed images of the breast.  Research in breast MRI started in 1980 in the USA and Germany.  MRI is highly sensitive and can detect abnormalities not seeing in either mammography or ultrasound.  In 1986, Heywang et al demonstrated that breast cancers enhance following gadolinium administration. In 1990, Kuhl et al published their study in the use of MRI in the screening of women at high risk for breast cancer, such as those with strong family history or genetic mutations like BRCA1 or BRCA2.

This post is dedicated to my friend and associate John Olsen MD who introduced the concept of mobile mammography and was the first who did stereotactic biopsies at Ohio State University.  He was the chief of Nuclear Medicine and Breast imaging at OSU and President of our departmental corporation URI.  I had the pleasure working with him during my tenure at OSU and learning from him on how to allay cancer patients fears.

Pionners; Dussik, Donald, Brown, Wild, Reid

 Ultrasound was first introduced in the practice of medicine approximately 90 years ago when Theodore Dussik and his brother Friederich attempted to use ultrasound to diagnose brain tumors.  In the ensuing time, ultrasound has become an important diagnostic modality in medicine.

Karl Theo Dussik (1908-1962) was born in Vienna, Austria and graduated from the University of Vienna Medical school where he worked as neurologist and psychiatrist.  Because of the difficulty in the diagnosis of brain tumors, Dussik, in 1937 started exploring the visualizatn of intracranial structures such as the ventricles with ultrasound. In 1945, Dussik together with his brother Friedrich constructed an apparatus and was able to visualise the brain and the ventricles. In 1947 he published his findings and thus is considered the "father of ultrasonic diagnosis" 

Ian Donald (1910-1987) was a Scottish physician who pioneered the use of ultrasound in obstetrics and gynecology. Donald graduated from the University of London in 1930.  During WWII he was drafted into the Royal Air Force during which time he developed an interest in radar and sonar.  After the war he became a Professor at Glasgow University where he explored the use of ultrasound in obstetrics in 1950 in collaboration with John MacVicar and Tom Brown an industrial engineer.  They developed the first compact contact ultrasound and were able to obtain an ultrasound image of a fetus. 

John J Wild (1914-2009) was an English-born American physician who received his medical degree from Cambridge in 1942 an immigrated to the United States in 1946 when he became a faculty at the University of Minnesota. Wild used ultrasound for body imaging notably for diagnosing cancer.  Modern ultrasonic medical scanners are descendants of the equipment Wild and his colleagues developed in 1950s.  In 1951 he and Dr. John Reid gained access to a unit that operated at the 15 MHz range, providing the detail needed to distinguish between healthy and cancerous tissues.  They were able to scan the breast and make the diagnosis of tumors by noninvasive means.  Reid and Wild developed tools for scanning the vaginal and rectal tissues.  Their work was published in the journal The Lancet in 1951 and in Science in 1952. They were credited as the first to develop equipment specifically designed for breast scanning and were able to differentiate between cystic and solid masses in the breast by means of ultrasonography. 

In the last 50 years due to technological advances, ultrasound units have changed from large machines to small user-friendly and sophisticated instruments.  Such evolution required contributions from the fields of physics, medicine and engineering.  Today ultrasound units are the sine qua non in the diagnosis of cardiac, abdominal musculoskeletal diseases and are also used in the guidance of interventional procedures. 

The post above is dedicated to Dr Nicholas Zannes who performed an ultrasound study on me recently for which I thank him. His contributions in radiology especially in the field of interventional radiology are noteworthy and help established the subspecialty in Greece.  In addition to being a good colleague I also thank him for being a good friend to me and my family for the past 50 years. 

Contrast Enhanced Ultrasound in Breast Cancer

Vraka et al published in vivo their research regarding the correlation of findings between contrast enhanced ultrasound (CEUS) and pathological and prognostic factors in breast cancer. 

They retrospectively analyzed 34 breast cancers on which CEUS studies were performed and they looked at qualitative findings and quantitative characteristics.

They found that indistinct tumor margins were characteristic of high-grade malignancy and also in estrogen negative tumors.  They also found that perilesional enhancement was seen in tumors positive for Ki-67 expression.  Finally, heterogeneous sentinel lymph node enhancement was associated with metastatic infiltration.

Although the authors suggested their study cohort was rather small, their findings correlated well with histopathological and prognostic factors used in the initial diagnosis and therapy of patients with breast cancer, the most common cancer in women. 

Sonographic criteria in the diagnosis and treatment of appendicitis.

According to a study by Xu et al published in the Journalof Ultrasound in Medicine ultrasound can provide information regarding the preferred treatment i.e. proceed with appendectomy or try antibiotics first in patients with appendicitis.

The authors reviewed retrospectively sonographic studies of 119 patients with histopathologically proven appendicitis.  The diagnostic criteria and the preferred treatment in patients with suspected appendicitis was the presence or absence of the normally echogenic submucosal layer, the presence of mural hyperemia, periappendiceal fluid, appendicoliths, and hyperechoic periappendiceal fat and the maximum outside diameter.

Thirty-two (27%) of the 119 patients had complicated appendicitis, including 11 with gangrenous appendicitis without perforation and 21 with gangrenous appendicitis and perforation. Loss of the submucosal layer was the only independent significant indicator of complicated appendicitis (P < .001) and provided sensitivity and specificity values of 100.0% and 92.0% respectively.

The researchers concluded if loss of echogenic submucosal layer was detected at sonograpy the diagnosis of complicated appendicitis was likely and, therefore, surgery was necessary. On the other hand, when ultrasound did not show loss of the submucosal layer, antibiotic therapy should be tried, as the likely diagnosis is uncomplicated appendicitis.

MRI and TRUS biopsy in prostate cancer

A paper by Ahmed et al published in the Lancet suggests a quarter of men suspected of having prostate cancer could avoid potentially dangerous biopsies with the help of MRI scans.

The authors did a multicenter study and tested the diagnostic accuracy of Multi-parametric MRI (MP-MRI) and Transrectal ultrasound guided prostate biopsy (TRUS-biopsy) against template prostate mapping biopsy (TPM-biopsy). Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy.  

The researchers enrolled 740 men, 576 of who underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsies.  Results from TPM-biopsy showed 408 (71%) of the men had cancer, including 230 (40%) men with clinically significant cancer.  When evaluating the 230 men with clinically significant cancer, the MP-MRI had correctly diagnosed 93% of the aggressive cancers, whereas TRUS-biopsy diagnosed only 48% as aggressive. This indicated that MP-MRI was more sensitive than TRUS-biopsy (P < .0001).  Of the 10 men with a negative MP-MRI scan, nine (89%) had no cancer or a harmless cancer.

However, TRUS-biopsy had greater specificity (96% vs. 41%) and positive predictive value (90% vs. 51%; P < .0001 for both) than MP-MRI.  Forty-four (5·9%) of 740 patients reported serious adverse events, including 8 cases of sepsis following biopsy.

This study shows that using the two tests could reduce overdiagnosis of harmless cancers by 5%, prevent one in four men from having an unnecessary biopsy, and improve the detection of aggressive cancers from 48% to 93%.

In conclusion given that prostatic cancer which is the most common cancer in men with about 176,000 new cases and the cause of death in 27,000 patients in the United States in 2013, MP-MRI is a promising diagnostic test in the effort to reducing over-diagnosis of clinically insignificant prostate cancers while improving the detection of clinically significant cancers.

Ultrasound is ineffective in the healing of bone fractures

A study published in the BMJ suggests that low-intensity pulsed ultrasound, used to speed healing of bone fractures, may be ineffective.

A randomized clinical trial that involved 501 patients who had surgical repair of fractures of the tibia found that patients treated with the low-intensity pulsed ultrasound (LIPUS) healed at the same rate as those given a sham treatment.

Patients self administer daily LIPUS (n=250) or use a sham device (n=251) until their tibial fracture showed radiographic healing or until one year after intramedullary fixation.

Primary registry specified outcome was time to radiographic healing within one year of fixation; secondary outcome was rate of non-union. Additional protocol specified outcomes included short form-36 (SF-36) physical component summary (PCS) scores, return to work, return to household activities, return to ≥80% of function before injury, return to leisure activities, time to full weight bearing, scores on the health utilities index (mark 3), and adverse events related to the device.

Results showed no impact on SF-36 PCS scores between LIPUS and control groups or for the interaction between time and treatment; minimal important difference is 3-5 points or in other functional measures. There was also no difference in time to radiographic healing. There were no differences in safety outcomes between treatment groups. Patient compliance was moderate; 73% of patients administered ≥50% of all recommended treatments.

It was concluded that postoperative use of LIPUS after tibial fracture fixation does not accelerate radiographic healing and fails to improve functional recovery.

Ultrasound in Elbow Fractures.

Avci et al published in the American Journal of EmergencyMedicine findings of their study of point-of-care ultrasound (POCUS) and computed tomography (CT) for patients presenting with elbow injuries in emergency departments. 

The authors examined 49 patients aged 5 to 65 years, who had at least 1 fracture of the elbow joint bones, and underwent CT scanning in emergency room. Patients were first evaluated with direct radiography, and then with POCUS by trained emergency physicians. Emergency physicians made treatment decisions based on the ultrasonography results. Then, CT scans were performed and were interpreted by radiologists. Orthopedic surgeons made treatment decisions based on the CT interpretations.

Of the 49 patients with elbow injury were included in the study 18 (37%) were women, and 31 (63%) were men. Compared with CT, sensitivity, specificity, positive predictive value, and negative predictive value of POCUS in fracture detection were 97%, 88%, 94%, and 93%, respectively. Although the sensitivity and specificity of POCUS in the decision for reduction were 95% and 100%, respectively, it was 93% and 100% in the decision for surgery.

The authors concluded that POCUS is effective in the diagnosis and management of elbow fractures when direct radiology is inconclusive and CT is required.

MRI in Cirrhotic Patients at High Risk for Hepatocellular Carcinoma

Kim at al reported in JAMA Oncology their experience regarding the accuracy of MRI with liver specific contrast versus ultrasonography in the surveillance of patients with cirrhosis who are at high risk in developing hepatocellular carcinoma.

Ultrasonography (US) is considered the study of choice for screening patients with cirrhosis at risk of hepatocellular carcinoma.  The current recommendation is for US to be performed every 6 months.

Liver MRI was performed on a 1.5Tesla scanner and Gadoxetic acid (Primovist) was administered at a dose of 0.025 mmol/kg.  Axial T1 weighted images of the arterial, portal, delayed and hepatobilliary phases at 4-mm thickness sections were obtained.   

The authors conducted a prospective study of 407 cirrhotic patients who underwent semi-annual US and MRI studies.  The patients were followed with dynamic computed tomography 6 months after the screening imaging studies.

A total of 407 patients received 1100 screenings with both MRI and US.  Hepatocellular carcinomas were diagnosed in 43 patients.  Ultrasound diagnosed only one HCC, MRI detected 26, 11 by both, and 5 were missed by both.

The HCC detection rate of the MRI was 86%, higher than the 27.9% of US.  MRI showed significantly lower false-positive findings than US, 3% versus 5.6% of US.  Of the 43 patients with HCC 32 had a single less than 2 cm nodule and received curative treatments.  The 3-year survival of the patients with HCC (86%) was at par to those without HCC.

The 5-year survival rate of HCC is lower than 20%, and early diagnosis is essential for the possibility of a cure.  The current recommendation for patients at high risk of developing HCC is US needs to be reviewed as the  accuracy of US is low.

The authors conclude that screening of patients with cirrhosis with MRI and liver specific contrast resulted in higher HCC detection rate and fewer false positive findings when compared with US.

JAMA Oncology, Online First, September 22, 2016