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.

Pioneers; Purcell, Bloch, Mansfield, Damadian, Lauterbur

In 1946 Edward Purcell (1912-1977) and Felix Bloch (1905-1983) independently discovered Nuclear Magnetic Resonance (NMR) which is the basis for Magnetic Resonace Imaging (MRI).  In 1952 Purcell and Block shared the Nobel Price in Physics for their discovery.

Peter Mansfield (1933–2017) was an English physicist and a Professor at the University of Nottingham shared the 2003 Nobel Prize in Physiology or Medicine with Paul Lauterbur, for discoveries concerning (MRI).  His Echo Planar Imaging (EPI) method allowed later techniques like fMRI, diffusion ,DTI and perfusion to be developed. 

Raymond Damadian (1936-2022) an American physician and inventor of the first MRI machine.  In a 1971 paper in the journal of Science professor Damadian reported that tumors can be detected in vivo by nuclear magnetic resonance because of much longer relaxation times (which means the return of a perturbed system into equilibrium) than normal tissues and suggested that these differences can be used to detect cancers. Damadian perfomed the first full body scan in 1977.

Professor Paul C Lauterbur (1929-2007) was awarded the Nobel Prize in 2003 in Physiology or Medicine for his ground breaking research in the department of Chemistry at Stony Brook University that led to the invention of magnetic resonance imaging.

The above post is dedicated to my colleagues and prominent neuro-radiologists, Drs Don Chakeres, Eric Bourekas, Greg Christoforidis who worked with me during my tenure as Radiology Chairman at Ohio State University and Stathis Gotsis PhD whith whom I collaborated at the University of Illinois in Chicago and who introduced  NMR in Greece. 

Ultra-low Field MRI

 An Ultra low field (ULF)  prototype magnetic resonance imaging (MRI) scanner that does not require heavy shielding and is much quieter than commercially available MRI scanners was developed by Wu et al in the University of Hong Kong.  The prototype system described in Physics World has 0.055 Tesla permanent samarium-cobalt (SmCo) magnet with a 29x70 cm gantry for patient access. Costing an estimated $20,000 to build, it would be significantly less expensive that the MRI scanners in use today which cost between $1 and $3 million.  The researchers hope that the ULF scanner, which can be plugged in a typical wall outlet, although it generates a magnetic field of a much lower strength than those produced by clinical MRI machines in use today might one day bring this valuable clinical tool to 70% of the world's population that does not have access to MRI imaging and thus improve global access to neuroimaging.

Cardiac MRI in the Assessment of Pulmonary Hypertension

Cardiac Magnetic Resonance Imaging (CMR) is an effective tool for evaluating patients with pulmonary arterial hypertension (PAH), according to a new meta-analysis published in JACC: Cardiovascular Imaging.

The study's authors analyzed data from 22 different studies, covering nearly 2,000 patients with pulmonary hypertension.  There were 18 clinical worsening events and 8 deaths per 100 patient-years.

The researchers determined CMR to be a powerful tool for predicting clinical worsening in PHA patients, with every 1% decrease in right ventricular ejection fraction associated with a 4.9% increase in the risk of clinical worsening over the next 22 months and a 2.1% increase in the risk of mortality over the next 54 months.

The authors concluded that CMR can effectively predict clinical worsening in PHA patients.   

Brain MRI Findings in Patients with Severe COVID-19

A study published in Radiology found that patients with COVID-19 infection exhibit abnormal brain findings other than stroke on MRI. 

The investigators looked at findings from thirty men and seven women whose mean age was 61 years who met the inclusion criteria. The researchers observed the following; signal abnormalities in the medial temporal lobe were noted in 43% of the patients;  30% of the patients had non-confluent multifocal white matter hyperintense lesions on fluid-attenuated  inversion recovery and diffusion sequences, with variable enhancement, with hemorrhagic lesions (30%); and extensive isolated white matter microhemorrhages (24%). The patients with the worse prognosis were those with brain hemorrhage.

                                   

The researchers concluded that patients with severe Covid-19 who did not have ischemic cerebral infarcts had abnormal MRIs with a wide range of findings.

DWI-MRI Predicts Breast Cancer Response to Treatment

Diffusion-weighted MR images (DWI_MRI) acquired 12 weeks after the start of neoadjuvant chemotherapy for breast cancer may provide the best indication of how patients will respond to treatment, according to a study published in Radiology.

The researchers analyzed 242 participants who were randomized to receive 12 weekly doses of paclitaxel with four cycles of anthracycline.   The MRI protocol included, DWI imaging T2-weighted and contrast enhanced sequences.

  

The authors concluded that after 12 weeks of therapy, change in breast tumor apparent diffusion coefficient at MRI predicts complete pathologic response to neoadjuvant chemotherapy

AI can diagnose Myocardial Infarction on non-enhanced MRI

A retrospective study of 212 patients published in Radiology used deep learning (AI) to identify and delineate chronic myocardial infarction without late gadolinium enhancement.

The model extracted motion features from the left ventricle on non-enhanced cardiac cine MRI and its per-segment sensitivity and specificity was 90% and 99 percent, therefore deep learning on non-enhanced cine cardiac MRI data can detect the presence and extent of chronic myocardial infarction. 

This approach has the potential to reduce the use of gadolinium contrast administration in patients with renal impairment, which is common in patients with coronary artery disease.

Breast MRI Improves depiction of DCIS Components

A study by Kuhl et al published in Radiology found magnetic resonance imaging (MRI) of the breast improves depiction of ductal carcinoma in situ (DCIS) components of invasive breast cancers prior to surgery.

The authors performed a prospective two-center study of 593 patients with biopsy proven invasive breast cancer that underwent breast MRI in addition to conventional imaging. 

The outcomes showed surgical-pathologic evaluation demonstrated DCIS components in 139 (23%) women. MRI had significantly higher sensitivity in the diagnosis of DCIS components pre-operatively in (84%; 118 women out of 139) than that of conventional imaging, which detected (36%; 51 of the 139 women). More than 50 percent of DCIS components were detected with MRI alone. 

The researchers also found the sensitivity benefits of MR imaging over conventional imaging improved with increasing relative size, and with increasing nuclear grade of DCIS components. Positive margin rates were generally low and did not diverge significantly between the 139 women with DCIS components versus the 454 women who lacked them.

The authors concluded that breast MRI improves depiction of DCIS components of invasive breast cancers before surgery.

Abbreviated Prostatic MRI

Kuhl et published in Radiology findings of their study in which they explored the accuracy of an abbreviated MRI of the prostate.  Multi-parametric contrast-enhanced MR imaging was performed in men with elevated PSA who after negative transrectal US-guided biopsy underwent state-of-the-art, full multiparametric contrast-enhanced MR imaging at 3.0-T that included high-spatial-resolution structural imaging in several planes, diffusion-weighted imaging at 0, 800, 1000, and 1400 mm²/sec, and dynamic contrast-enhanced MR imaging, obtained without endorectal coil within 34 minutes 19 seconds.

One of four radiologists first reviewed only two sequences of the study

 consisting of single-plane (axial) structural imaging (T2-weighted turbo spin-echo and diffusion-weighted imaging), acquired within 8 minutes 45 seconds (referred to as bi-parametric MR imaging), and established a diagnosis; only thereafter, the remaining full multiparametric contrast-enhanced MR images were read. Men with PI-RADS categories 3–5 underwent MR-guided targeted biopsy. Men with PI-RADS categories 1–2 remained in urologic follow-up for at least 2 years, with rebiopsy (transrectal US-guided or transperineal) when appropriate. 

A total of 542 men, aged 65 years with median PSA of 7 ng/mL, were included. Bi-parametric MR imaging helped detect clinically significant prostate cancer in 138 men. Full multi-parametric contrast-enhanced MR imaging allowed detection of one additional clinically significant prostate cancer (a stage pT2a, intermediate-risk cancer with a Gleason score of 3+4) and caused 11 additional false-positive diagnoses. Diagnostic accuracy for detection of clinically significant cancer of bi-parametric MR imaging was 89.1% (483 of 542) was similar to that of full multi-parametric contrast-enhanced MR imaging 87.2% (473 of 542). 

The authors concluded that bi-parametric MR imaging which can be done with two sequences and without contrast injection in less that 9 minutes allows for detection of clinically significant prostate cancer with a rate equivalent to conventional full multi-parametric contrast-enhanced MR imaging protocols.

FDA requires a warning on Gadolinium Contrast Agents

The U.S. Food and Drug Administration (FDA) has issued a new advisory requiring a new class warning and other safety measures for all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) regarding gadolinium remaining in patients’ bodies, including the brain, for months to years after receiving these drugs which may be linked to renal harm.   These agents have been associated with nephrogenic systemic fibrosis in patients with pre-existing renal failure.  Although this complication is rare, it is serious enough to justify the advisory to all professionals and patients.

Although the benefit of all approved GBCAs continues to outweigh any potential risks the FDA now requires several actions to alert health care professionals and patients about gadolinium retention after an MRI using a GBCA, including actions that can minimize problems.  Health care professionals should consider the retention characteristics of each agent when choosing a GBCA for patients who may be at higher risk for gadolinium. These patients include those requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions. FDA suggests fewer repeated GBCA imaging studies when possible, particularly closely spaced MRI studies. However, physicians are advised to not avoid or defer necessary GBCA MRI scans.

Patients, parents, and caregivers should carefully read the new patient Medication Guide that will be given to him before receiving a GBCA. The Medication Guide explains the risks associated with GBCAs.  It also asks the patient to inform health care professional about medical conditions, such as: pregnancy, date of last MRI and number of prior MRI with gadolinium and kidney problems.

All new patients will be provided with the Medical Guide that provides educational information that every patient will be asked to read before receiving a GBCA. FDA will also require manufacturers of GBCAs to conduct human and animal studies to further assess the safety of these contrast agents.

MRI safe for most patients with Pacemakers or Defibrillators

A study by Russo et al published in the NEJM found that MRI scans for patients with older not FDA approved pacemakers and implantable cardioverter-defibrillators (ICD) are safe even if the scan focuses on the chest area.

The researchers performed 1000 MRI in which patients had a pacemaker and in 500 MRI in which patients had an ICD in a 1.5T MRI scanner. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI.  Nine of the implants were disrupted but reset themselves to backup mode.  In all but one instance the effect was temporary.

Neither MRI performed on chest or in other parts of the body produced significant complications.   The concerns of potential magnetic field–induced cardiac lead heating, which could result in myocardial thermal injury and/or disrupt pacing properties of the devices were noted in this study.

The authors concluded that in their study, device or lead failure did not occur in any patient who was appropriately screened, and had the device reprogrammed in accordance with the pre-specified protocol.

Breast MRI is the study of choice for women at high risk for breast cancer.

According to a study published in Radiology Lo et al reviewed the outcomes of 3,934 screening breast studies (MRI and mammograms) performed on 1,249 high-risk women. A total of 45 cancers (33 invasive and 12 ductal carcinomas in situ) were diagnosed, 43 were seen with MR imaging and 14 with both mammography and MR imaging.   The cancer detection rate for MR imaging was 21.8 cancers per 1000 examinations and that for mammography was 7.2 cancers per 1000 examinations. Sensitivity and specificity of MR imaging were 96% and 78% respectively, and those of mammography were 31% and 89%, respectively (P < .001).  The researchers reported that all cancers found at screening mammography were also detected on breast MRI.  

The researchers concluded that annual screening mammography adds no value to women that are at high risk for breast cancer especially since they are screened each year with breast MRI.

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.