The New York Times reported Friday that the center, which is part of Columbia University, had used at least 10 batches of drugs that violated Food and Drug Administration regulations since 2007. Former employees told the Times that the center was under such pressure to produce studies that it cut corners by hiding impurities in drugs despite FDA warnings—even forging at least one document.

“These are not the actions of a rogue, but instead are systematic forgeries condoned and approved by the lab director,” said one employee in a 2009 resignation letter.

Like many laboratories, the Kreitchman Center made its own radiotracers (drugs that emit low-level radiation and are engineered to accumulate in specific areas of the body that are targeted for PET scans) because the compounds degrade quickly. The FDA regulates the allowable radiation levels and the purity of the drugs. Impurities—unknown chemicals created or introduced during the manufacturing process—may or may not harm the patients. (Columbia in fact said it had conducted its own investigation and reported to the FDA on July 6 that it had found no evidence that patients had been harmed.)

However, the impurities might also compromise the research—especially the kind of brain research that the Kreitchman Center has been doing. Impure drugs targeting receptors in the brain could have unpredictable effects on mood or behavior.

“We acknowledge serious shortcomings of quality control in the manufacturing process and record-keeping at this lab,” David I. Hirsch, PhD, Columbia’s executive vice president for research, told the Times. “That is why we are fundamentally reorganizing the lab’s management and operations in response to what the FDA told us.”

Neither the FDA nor Columbia publicized the investigations or their consequences. The Times said it learned of them from “doctors who were familiar with the lab’s problems.”

The Kreitchman Center has received millions of dollars over the years from the federal government and pharmaceutical companies to use brain imaging to study patients with such disorders as schizophrenia and severe depression.

Already, law firms are trolling for potential clients among the lab’s research subjects. Here’s just one that is “aggressively investigating potential lawsuits and legal claims relating to research misconduct perpetrated by the Kreitchman Center and Columbia University.”

Dr. Hirsch said that “when manufacturing resumes under new leadership, it will meet the strictest standards and best practices for ensuring the quality” of the drugs the lab makes. He said the clinical (nonresearch) side of the Kreitchman Center was “fully approved and operational” and remained open for patient care.

As for the lab’s reputation and the validity of its research, Barry Siegel, MD, chairman of the Radioactive Drug Research Committee at Washington University in St. Louis, told the Times: “If you’re exposing people to radiation and getting garbage data, then that becomes an ethical problem.”

Related seminar: Radiology Review (discount expires next week)

The researchers, from Washington University School of Medicine in St. Louis, noticed this while looking into something entirely different: the long-term effects of premature birth on brain development. They published their findings online this week in the Proceedings of the National Academy of Sciences.

First author Jason Hill, an MD/PhD student, compared MRI brain scans of 12 full-term infants to scans from 12 healthy young adults.

He and the other researchers found that the cerebral cortex—the wrinkled area on the brain’s surface that’s responsible for higher mental functions—grows unevenly. As the brain matures, every region of the cortex expands. But one quarter to one third of the regions expand twice as much as the other cortical areas.

“Through comparisons between humans and macaque monkeys, my lab previously showed that many of these high-growth regions are expanded in humans as a result of recent evolutionary changes that made the human brain much larger than that of any other primate,” said senior author David Van Essen, PhD. “The correlation isn’t perfect, but it’s much too good to put down to chance.”

Dr. Van Essen is Edison professor and head of the Department of Anatomy and Neurobiology. He was quoted in a university news release.

The high-growth areas are linked to advanced mental functions such as language and reasoning. Dr. Van Essen speculated that physical growth in these areas may be delayed so that they can be shaped by early life experiences.

Terrie Inder, MD, PhD, professor of pediatrics and another study author, offered another possible explanation. She noted that infant brain size is limited by the need to pass through the mother’s pelvis at birth and suggested that the brain therefore must prioritize.

“Vision, for example, is a brain area that is important at birth so an infant can nurse and learn to recognize his or her parents,” Dr. Inder said. “Other areas of the brain, less important very early in life, may be the regions that see greater growth as the child matures.”

The researchers are now conducting similar scans of premature babies at birth and years later. “Preterm births have been rising in recent years, and now 12 percent of all babies in the United States are born prematurely,” Dr. Inder said. “Until now, though, we were very limited in our ability to study how premature birth affects brain development because we had so little data on what normal brain development looks like.”

Related seminar: Neuro & Musculoskeletal Imaging (will be released soon; available for order now)

CT is the de facto standard for stroke diagnosis. But newer MRI techniques, such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI), are more accurate, the article said.

“While CT scans are currently the standard test used to diagnose stroke, the academy’s guideline found that MRI scans are better at detecting ischemic stroke damage compared to CT scans,” said lead guideline author Peter Schellinger, MD, of the Johannes Wesling Clinical Center in Minden, Germany. Schellinger was quoted in an academy news release.

Ischemic strokes (resulting from lack of blood flow to the brain rather than hemorrhage) constitute about 87 percent of all strokes. In the United States, stroke is the third-leading cause of death and the leading cause of permanent disability.

The new guideline resulted from a study in which a team of neurologists, neuroradiologists, and radiologists analyzed literature dating from 1966 to January 2008. They particularly cited a study that compared the accuracy of CT and DWI in 356 consecutive potential patients at a hospital emergency department over an 18-month period. Two neuroradiologists and two stroke neurologists, blinded to clinical information and CT-DWI pairings, interpreted the scans independently.

According to the article:

In the subset of 221 patients scanned within 12 hours of onset, the majority of readers correctly diagnosed acute ischemic stroke by MRI more often than by CT (94 vs. 22).

The study also found that MRI more accurately detected lesions from stroke and helped identify the severity of some types of stroke or diagnose other conditions with similar symptoms.

“This guideline gives doctors clear direction in using MRI first, ultimately helping people get an acute stroke diagnosis and treatment faster,” said Dr. Schellinger. “However, one situation in which CT may still be used first is when a person needs an emergency injection of drug therapy (also known as intravenous thrombolytic therapy) to break up blood clots, if MRI is not immediately available, to avoid delays in starting this treatment. MRI can be added later if more information is needed. Otherwise, MRI should be used first.”

Related seminar: National Diagnostic Imaging Symposium

Mary L. Phillips, MD, presented her findings at the Royal College of Psychiatrists’ International Congress in Edinburgh, Scotland, last month. She is professor of psychiatry and director of the Clinical and Translational Affective Neuroscience Program at the University of Pittsburgh School of Medicine and professor of neuroscience and emotion at the Institute of Psychiatry in London.

Regarding BPD, Dr. Phillips said, “Only one in five sufferers are correctly diagnosed at first presentation to a doctor, and it can take up to 10 years before sufferers receive a correct diagnosis.”

She explained: “The problem is that sufferers frequently fail to tell their doctors about hypomanic phases because they can be experienced as quite pleasant or judged not to be abnormal at all.”

Research at the University of Pittsburgh had shown that BPD may soon be accurately diagnosed with a combination of functional MRI, which scan’s the brain’s neural pathways, and DTI (diffusion tensor imaging), which scan’s the brain’s white matter.

Dr. Phillips conducted a study using MRI to compare brain function in two groups of people, one with BPD and one with depression. She found that the two could be distinguished “by a very different and distinct pattern of brain activity.”

She added: “If there’s a plan to do just one MRI in the future to try to decide whether someone has bipolar or depression, I’d suggest the right prefrontal cortex. If there is any abnormality in functioning between the right and prefrontal cortex and right amygdala, the chances are that the person has bipolar.”

She suggested that MRI scans might also be used to predict the future onset of BPD in young people who have not yet shown symptoms of the disease.

Related seminar: Head To Toe Imaging

The research was part of a larger study called the Alzheimer’s Disease Neuroimaging Initiative. The results have been published in the journal Neurology.

The researchers identified 85 people with mild cognitive impairment (MCI), which is defined by the Alzheimer’s Association as “a condition in which a person has problems with memory, language or another mental function severe enough to be noticeable to other people and to show up on tests, but not serious enough to interfere with daily life.” It’s often, but not always, an Alzheimer’s precursor.

Each patient received an episodic memory test (involving recall of word lists), a blood test for a specific form of the APOE gene that is associated with Alzheimer’s, an MRI brain scan to measure the size of the hippocampus, a measurement of tau or beta-amyloid proteins (thought to play a role in Alzheimer’s), and a PET brain scan.

“Each of these tests have independently shown promise in predicting disease progression,” said study author Susan M. Landau, PhD. “However, prior to the Alzheimer’s Disease Neuroimaging Initiative, they had never been compared to one another in the same study before.”

Dr. Landau, of the Helen Wills Neuroscience Institute at the University of California, Berkeley, and a member of the American Academy of Neurology, was quoted in a press release from the academy, which publishes Neurology.

After the tests, participants were followed an average of 1.9 years. During that time, 28 of them developed Alzheimer’s. Those who showed abnormal results on both the PET scans and the episodic memory tests were nearly 12 times more likely to develop the disease than those who scored normally on both measures.

Dr. Landau acknowledged the PET cost issue, but told HealthDay News: “However, we think where it might be feasible to use imaging is in the process of selecting participants for clinical trials for potential Alzheimer’s drugs. Because we want to identify the right people who can ideally benefit from these drugs.”

She added: “Outside of that, people have imaging done, even though it’s expensive, for lots of medical conditions. So if it’s useful enough, it could be promising nevertheless.”

Related seminar: Neuroradiology Review

Two radiology technicians have sued Bozeman Deaconess Hospital in Bozeman, Montana. They claim that, while working in a darkroom at the hospital, they were exposed to unsafe levels of X-ray film developing chemicals.

Court documents say one of the women began working at the hospital in 2000 and the other in 2007. Both women say that within a short time, they began experiencing fatigue, headaches, and other symptoms. In the court documents, they say they were exposed to “unhealthy and toxic levels of Glutaraldehyde and other harmful chemical gases associated with developing X-ray film.”

The documents claim that on May 20, 2009, maintenance workers discovered that the ventilation fan in the darkroom was not plugged in and had never operated. In the documents, the women say that because of the “dangerous chemicals” in the unventilated room, they suffered damages including “physical injuries, medical expenses, lost earning capacity, lost wages, pain and suffering, mental, physical and emotional distress, loss of established course of life, loss of household services and other injuries.”

According to the federal Occupational Health and Safety Administration (OSHA), glutaraldehyde is used in X-ray developing solutions as a hardening agent to shorten film drying time. The OSHA publication Best Practices for the Safe Use of Glutaraldehyde in Health Care says, “The most serious adverse health effect documented among employees exposed to glutaraldehyde vapor is occupational asthma, a chronic condition characterized by bronchial hyperresponsiveness.” There are no mandatory federal exposure limits, but the National Institute for Occupational Safety and Health recommends a maximum exposure limit of 0.2 parts per million.

The hospital responded: “Bozeman Deaconess Hospital voluntarily requested an on-site safety consultation in June 2009 by the Montana Occupational Safety and Health Bureau. The State of Montana’s representative reported that ‘[n]o hazards were found during the visit to Bozeman Deaconess Hospital’ in the area in question.”

The hospital said it would defend itself against the suit but declined to elaborate, citing its policy not to comment in detail regarding pending litigation.

Related seminar: The Business of Radiology

So conclude two researchers who undertook a systematic review of 19 prospective studies involving 6,438 patients. Shauna Runchey, MD, and Steven McGee, MD, both of the University of Washington Department of Medicine in Seattle, published their findings this month in the Journal of the American Medical Association.

Distinguishing between the two types of stroke can be crucial. If it’s ischemic (caused by an interruption in blood supply), then a blood clot is often the culprit, and immediate thrombolysis treatment can break up the clot and minimize damage. But if it’s caused by hemorrhage, then thrombolysis can make things worse.

The various studies looked at markers of hemorrhagic stroke. For example, the likelihood that the stroke was hemorrhagic increased 6.2-fold if the patient was in a coma, 5.0-fold if neck stiffness was present, 4.7-fold if there were seizures, 4.3-fold if diastolic blood pressure exceeded 110 mmHg, 3.0-fold if there was vomiting, 2.9-fold if there was a headache, and 2.6-fold if the patient lost consciousness.

The Siriraj score, which encompasses some of the above factors as well as others, such as the presence of diabetes, also helped distinguish the two types of stroke. Patients were 5.7-fold more likely to have hemorrhagic stroke if they had a score higher than 1 and 71% less likely if they had a score lower than -1. However, Drs. Runchey and McGee noted that about 20% of patients have scores between 1 and -1, which they termed “diagnostically unhelpful.”

One study found that clinicians’ overall impressions were as accurate as the Siriraj score in diagnosing hemorrhagic stroke.

However, Drs. Runchey and McGee say, “Neither the clinical impression of experienced clinicians nor the most accurate stroke score can improve the post-test probability of hemorrhage to greater than 50%.” They conclude:

While combinations of findings are more predictive than individual findings, diagnostic certainty requires neuroimaging.

Related seminar: State-of-the-Art Imaging and Interventional Radiology

A team led by researchers at Johns Hopkins Children’s Center in Baltimore explored those questions. Unfortunately, the researchers didn’t come up with easy answers. They did say that doctors had better decide on a plan in advance, before meeting with parents to discuss a child’s brain MRI results. (The researchers aimed their advice primarily at pediatricians, but radiologists will likely be dragged into the discussion at some point.)

Here’s the scenario: A child undergoes brain MRI. The findings reveal an unexpected but benign—or at least nonemergency—anomaly. (In the Hopkins study of 953 children ages 5 through 14, that happened with 63 of the children, or 6.6%.) What do you tell the parents?

“Doctors need to figure out what, if anything, they want to share with patients about such findings because they seldom require urgent follow-up,” said senior investigator John Strouse, MD, PhD, a hematologist at Hopkins Children’s. The report by Strouse and his team was published online last week in the journal Pediatrics.

According to the researchers, the most common reasons for brain MRI in children are seizures, headaches, and enrollment in a medical study that requires such testing as a prerequisite. The patients in the Hopkins study all had sickle cell disease; most were African-American. They were being screened for participation in a sickle cell research study.

The researchers emphasized that none of the brain anomalies were related to sickle cell disease, suggesting that the findings may apply to healthy children in general.

Of the 63 children with abnormal brain findings, none required emergency treatment. Only six needed follow-ups classified as urgent (for possible slow-growing tumors or Chiari malformation type 1, in which brain tissue extends into the spinal canal). Two of the children in the “urgent” category underwent surgery within the following six months. Twenty-five children required routine follow-up for spinal cord anomalies or a less-serious subtype of Chiari malformation. Thirty-two children required no follow-up at all for a benign anomaly called cavum septum pellucidum, in which a thin membrane separates the brain’s lateral ventricles.

Obviously, you tell parents about the “urgent” findings. But what about the benign anomalies? Should a parent know, just in case, even if there’s no clear clinical importance—and if conveying the information may lead to unnecessary tests and equally unnecessary fear?

Hopkins quoted Dr. Strouse as saying that the study highlights a need for practices to work out guidelines for such situations in advance and for physicians to prepare for such discussions with parents. Otherwise, he said, some pediatricians simply avoid discussion of the anomalies altogether and refer the patient to a neurologist or neurosurgeon—thus inevitably giving rise to additional fear and anxiety.

Lori Jordan, MD, PhD, a pediatric neurologist at Hopkins Children’s and lead investigator for the study, described the quandary this way:

Helpful as it is, imaging technology can open a Pandora’s box, sometimes showing us things we didn’t expect to see and are not sure how to interpret.

Related seminar: Review for Practicing Radiologists

So concludes a group of German researchers who undertook “a selective literature review on recent technical innovations in the field of WB-MRI and the clinical uses of this new method, with particular emphasis on diagnostic imaging in oncology.” Their findings appear in the current issue of Deutsches Ärzteblatt International.

Here are some specific uses the researchers examined, along with their conclusions:

• Tumor screening. Because it does not involve ionizing radiation, WB-MRI may have some potential for screening of general, asymptomatic populations—but its time has not yet come, because of the low percentage of patients in which tumors were detected (less than 2%) and the lack of proven cost-effectiveness.
• Tumor staging. WB-MRI appears particularly effective in TNM staging of patients with gastrointestinal tumors, breast cancer, or malignant melanoma (diagnostic accuracy of 91%). It seems less effective in detecting lymph node or lung metastases or the staging of pulmonary tumors.
• Multiple myeloma and other bone-marrow diseases. Because of its good bone-marrow contrast, WB-MRI may be the best choice for detecting plasma cell neoplasms, particularly in early stages of the disease.
• Rheumatic diseases. MRI provides especially useful information in the early stages of rheumatic joint disease. Because rheumatoid arthritis can affect the whole body, WB-MRI might find early manifestations of this disease.
• Diabetes. “WB-MRI seems suitable for early diagnosis of secondary complications and for potentially more effective treatment planning in patients with diabetes mellitus, who have a high prevalence of cardiovascular diseases.”
• Benign bone tumors. Patients with multiple cartilaginous exostoses face considerable risk that the tumors will transform from benign to cancerous. WB-MRI can be particularly helpful in these cases because osteochondromas often occur in many different areas of the body and because many patients are young and thus would be at higher risk from repeated radiation exposure.

Technical advances now allow WB-MRI to be completed in less than an hour without loss of image quality. It seems likely that we’ve just started exploring its usefulness.

Related seminar: Head To Toe Imaging

A summary of the research just published in the journal Neuron describes how the team used pulsed ultrasound to stimulate not only action potentials (nerve impulses) but also motor responses in the brains of mice—without any kind of surgery. In fact, said lead author Yusuf Tufail, pulsed ultrasound “elicits motor responses comparable to those only previously achieved with implanted electrodes and related techniques.”

He added: “It is fascinating to witness these effects firsthand.” Even more fascinating are some of the team’s other discoveries. Its experiments with deeper brain circuits revealed that ultrasound may be able to modify cognitive abilities.

“We were surprised to find that ultrasound activated brain waves in the hippocampus known as sharp-wave ripples,” Tufail was quoted as saying in an Arizona State news release. “These brain activity patterns are known to underlie certain behavioral states and the formation of memories.”

Dr. Tyler said he thinks ultrasound eventually may be able to enhance cognitive performance and possibly treat such cognitive disabilities as mental retardation and Alzheimer’s disease.

The technique appears to be safe; the team found that repeated low-intensity ultrasound had no negative effects on the mice.

Dr. Tyler thinks there may be mind-boggling applications beyond medicine and science. He envisions ultrasound as a core platform for future interfaces between brain and machine that could be used for gaming, entertainment, and communication. For example, he said:

Maybe the next generation of social entertainment networks will involve downloading customized information or experiences from personalized computer clouds while encoding them into the brain using ultrasound. I see no reason to rule out that possibility.

Wow. “To be honest,” Dr. Tyler said, “we simply don’t know yet how far we can push the envelope. That is why many refer to the brain as the last frontier. We still have a lot to learn.”

Related seminar: Radiology Review (new; $200 discount expires soon)