NERVECENTERMAY 2010MAY 2010

Continuing the Debate Over CT RadiationExposure: Former FDA Scientist-Reviewer ClaimsWarnings Ignored

A former contractor for the US Food and Drug Ad-ministration (FDA) revealed at a public meeting onmedical equipment radiation risks that the FDA didnot renew his contract with the agency because he op-posed wider use of computed tomography (CT), andthat managers repeatedly ignored his and other agencyscientists’ concerns about potential radiation risks fromequipment being considered for approval.

Julian Nichols, a gastroenterologist, said his contractwas allowed to lapse after he took a stance against ap-proving the use of CT scans for routine colon cancerscreening. Nichols, who now works at the ScrippsClinic Rancho Bernardo, in San Diego, Calif., said heunsuccessfully argued with FDA officials that suchscreening would needlessly expose patients to excessivedoses of radiation.

He and others became concerned while reviewingthe application for a virtual colonoscopy device thatthey believed would deliver a radiation dose that couldprove dangerous, but were “pressured” into changingtheir recommendations.

According to Nichols, “FDA physicians and scien-tists were ridiculed and chastised for raising the buga-boo of radiation.”

The New York Times reported that it had obtaineddocuments confirming that Nichols and others ob-jected to plans to approve the application by GeneralElectric (GE). That application remains under review.

The FDA’s March 30-31 meeting was held to hearindustry representatives’ and hospital groups’ testimo-nies on the adequacy of current standards and proce-dures to protect patients and health care workers frompotential radiation risks from imaging devices, includ-ing CT scans and mammography equipment. An esti-mated 70 million CT sans are performed each year inthe US, according to the FDA.

A colleague of Nichols corroborated his allegations,telling the meeting that the agency should pay atten-tion to what the charges suggest.

“Science must not be ignored, suppressed or dis-

torted as that endangers the public,” said RobertSmith, a medical reviewer still working for the agencywho also opposed CT scaning for colon cancer.

In a statement, FDA spokesman Dick Thompsonsaid the agency’s inspector general looked into Nichols’retaliation allegations, but chose not to investigate.

“It is not uncommon for scientists, both internaland external to the agency, to disagree on the safetyand effectiveness of products under review or on thesteps needed to achieve public health goals,” accordingto the FDA statement.

The meeting was the latest development in a contro-versy that began in October 2009 (see NerveCenterAnn Neurol 2009;65(5):A7-A9), when it was learnedthat more than 200 brain scan patients at Cedars-SinaiHospital, in Los Angeles, were exposed to as much aseight times the acceptable radiation dose for such test-ing when the wrong protocols were entered on a GEmulti-slice CT unit. The accidental time-lapse expo-sures resulted in skin burns and hair loss in some pa-tients, and several lawsuits have been filed against thehospital.

An investigation at the hospital revealed that thescanner in question had been recalibrated incorrectlyseveral months before, and there had been some mis-understanding of a unit’s automated dose selection fea-tures. In addition, training of CT technologists wasfound to have been inadequate, and there was insuffi-cient surveillance of pre-selected unit dosing protocols.The hospital has since corrected the problems.

An additional 60 cases of overexposure were identi-fied at the hospital, and subsequent investigations bythe agency discovered other individual cases at severalother medical facilities. As many as 300 incidents havenow been documented, according to the agency.

The Cedars-Sinai CT unit was made by GE; how-ever, cases have involved more than one manufacturer,according to the FDA.

New GuidelinesIn response to concerns raised by these accidental over-exposures, the FDA issued interim guidelines last Feb-ruary, advising hospital radiation departments to re-

Contact Annals of Neurology, aon@ucsf.edu

© 2010 American Neurological Association A7

view their exposure procedures and CT scan settings,and to monitor radiation dosages more carefully foreach CT patient.

The program promotes safe use of radiation-emittingmedical equipment by providing support for informedclinical decision-making, and increasing patient aware-ness of total lifetime radiation exposure. The FDA isalso considering increased stricter monitoring require-ments for CT scanners and fluoroscopic devices, withmore safeguards and additional training of operators.

The initiative covers three types of medical imagingprocedures: CT, nuclear medicine studies, and fluoros-copy. According to the agency, these procedures are thegreatest contributors to total radiation exposure withinthe US population and use much higher radiationdoses than other procedures, such as X-rays or mam-mography.

“The amount of radiation Americans are exposed tofrom medical imaging has dramatically increased overthe past 20 years,” said Jeffrey Shuren, director of theFDA’s Center for Devices and Radiological Health, inannouncing the guidelines. “The goal of FDA’s initia-tive is to support the benefits associated with medicalimaging while minimizing the risks.”

According to the National Council on RadiationProtection and Measurements, total radiation exposureamong the general population in the US. has doubledover the last two decades, largely due to the increase inmedical imaging. Perfusion CT scans trouble some ex-perts because the radiation doses are much higher thanfor other imaging procedures. For example, the radia-tion dose associated with a CT abdomen scan is thesame as the dose from approximately 400 chest X-rays.In comparison, a dental X-ray calls for approximatelyone-half the radiation dose of a chest X-ray. Both di-agnostics serve important, sometimes critical, publichealth needs.

“The FDA is making progress in the investigation ofthis problem,” said Shuren. “While we do not knowyet the full scope of the concern, facilities should takereasonable steps to double-check their approach to CTperfusion studies and take special care with these im-aging tests.”

Through the FDA’s regulatory oversight of medicalimaging devices, such as CT scanners, and through col-laboration with other federal agencies and health careprofessional groups, the FDA is advocating the adop-tion of two principles of radiation protection: appro-priate justification of the radiation procedure and op-timization of the radiation dose used during eachprocedure.

“A single CT scan of the abdomen is roughly equiv-alent to the dose of 400 chest X-rays,” noted Shuren.“Working together, the FDA and other organizationshope to help patients get the right imaging exam, atthe right time, with the right radiation dose.”

The three-pronged initiative the FDA is announcingwill promote the safe use of medical imaging devices,support informed clinical decision-making, and in-crease patient awareness of their own exposure.

The FDA intends to issue targeted requirements formanufacturers of CT and fluoroscopic devices to incor-porate important safeguards into the design of theirmachines to develop safer technologies and to provideappropriate training to support safe use by practitio-ners.

The FDA has recommended that health care profes-sional organizations continue to develop diagnostic ra-diation reference levels for medical imaging proceduresand increase efforts to develop one or more nationalregistries for radiation doses. Such a dose registrywould pool data from many imaging facilities nation-wide, capturing dose information from a variety of im-aging studies. According to the FDA, such a repositorywould help to better define diagnostic reference levelswhere they do not yet exist, validate levels that do ex-ist, and provide benchmarks for health care facilities touse in individual imaging studies.

Reducing RiskThe March 30-31 meeting was held to solicit profes-sional input on what requirements need to be estab-lished, and by far the majority of comments endorsedefforts to reduce patient exposures.

Manufacturers of scanners defended their safety

New CT Guidelines for Research

The FDA now requires hospitals and research facili-ties to:

● Assess whether patients who have under-gone CT perfusion scans have received excessradiation.

● Review radiation dosing protocols for all CTperfusion studies to ensure the correct dosingfor each study performed.

● Implement quality control procedures to en-sure that dosing protocols are followed everytime, and that the planned amount of radiationis administered.

● Require that radiation technologists checkthe CT scanner display panel before performingany study to make sure the amount of radiationto be delivered is at the appropriate level for theindividual patient.

● Adjust the dose of radiation so it is appro-priate for each study if more than one study isperformed on a patient during one imagingsession.

ANNALS of Neurology

A8 Volume 67, No. 5

record at the hearing, while offering support for theFDA’s new initiative to reduce patient exposures.

“Reducing patients’ exposure to medical radiation hasbeen, and continues to be, a primary focus of the med-ical imaging industry. . .Our members have introducednew products and system innovations. . .that have re-duced radiation dose for many procedures by up to 75percent,” said Dave Fisher, executive director of theMedical Imaging and Technology Alliance (MITA),which represents all major medical imaging equipmentmakers.

MITA recently announced a new industry-widecommitment to address patient safety in medical imag-ing by ensuring that CT equipment includes additionalradiation safeguards. These will alert CT machine op-erators when radiation dose levels – as determined byhospitals and imaging centers – are being exceeded.The radiation dose upper-limit alert will notify opera-

tors when an error may have occurred in setting pa-rameters, and the feature can be configured to preventa scanner from being operated if levels are incorrect.

The American Association of Physicists in Medicine(AAPM) is a scientific and professional society com-prised of medical physicists who establish radiationmeasurement procedures and perform them on radia-tion emitting devices, including computed tomography(CT) scanners.

According to the AAPM, the trouble is not thatmedical imaging scanning is inherently dangerous, butthat too many unnecessary scans are being performed.

“Many CT scans are ordered without sufficient med-ical justification and the most efficacious way to reduceCT radiation levels to the US population is to substan-tially reduce unnecessary CT scans,” according to thegroup.Kurt Samson

LONG AGOin the Annals...NEUROFIBRILLARY TANGLES, GRANULOVACUOLAR DEGENERATION, AND NEURON LOSS IN DOWN SYNDROME: QUANTITATIVE

COMPARISON WITH ALZHEIMER DEMENTIA

BALL MJ, NUTTALL K

MAY 1980

ABSTRACT

The degree of neurofibrillary tangle formation, granulovacuolar degeneration, and nerve cell loss was quantified

in serial sections of the hippocampal formation from the brains of 5 adults dying with Down syndrome (mongolism).

These morphometric results were compared with values obtained from a series of mentally normal elderly patients

reported previously.

Granulovacuolar change appeared to be related as much to patient age as to the existence of mongolism. By

contrast, the number of Alzheimer neurofibrillary tangles and loss of pyramidal neurons from the hippocampus ex-

ceeded levels found in considerably older subjects and fell into the same range of severity as was noted in 8 patients

with Alzheimer dementia. The neuron population in the hippocampus of Down syndrome patients may be only half

the expected normal number for their decade.

These quantitative similarities stimulate the search for a common pathogenetic mechanism underlying cerebral

changes in mongolism and senile dementia of the Alzheimer type.

May, 2010 A9