Oldendorf's interest neuroimaging was precipitated by a dislike for invasive procedures (like pneumoencephalography and direct carotid puncture) that he performed as a clinical neurologist.
At UCLA, he started his seminal investigations into the two major lines of research that would define his career: X-ray shadow radiography and cerebral angiography.
Ingeniously, by using materials found in his home (such as his son's toy train, a phonograph turntable, and an alarm clock motor), Oldendorf demonstrated a method of producing cross-sectional images of soft tissue by back-projection and reconstruction.
In October, 1963 Oldendorf finally received a U.S. patent for a "radiant energy apparatus for investigating selected areas of interior objects obscured by dense material,".
Once these techniques became widely accepted, Dr. Oldendorf, along with William Markley McKinney, MD (1930–2003) were instrumental in promoting the use of Computed Tomography among neurologists to help decrease the use of superfluous and invasive tests.
Oldendorf's work in measuring blood flow with radioactive isotopes was fundamental to the subsequent development of techniques now used in many nuclear medicine laboratories.
These results have been essential in developing PET and SPECT imaging; in studying glucose transport and brain metabolism; and in characterizing clinically important diseases such as cerebral ischemia, starvation, and epilepsy.
Oldendorf's experiments were also the first to prove that cerebrospinal fluid functions as a "sink" in relationship to brain metabolism, a concept that is being investigated in relation to the pathophysiology of presenile dementias such as Alzheimer's disease.
He participated in the ad hoc committee that unanimously voted to form the Society for Computerized Tomography so as to continue its educational activities.
Broad wrote an article titled "The Riddle of the Nobel Debate" in which he posited that politics in Stockholm forced the removal of Dr. Oldendorf's name during the nomination process.
He was supposed to have remarked Naturally I'm disappointed; but I'll keep working and maybe one day I'll win a Nobel Prize for something else--if I live long enough.He died unexpectedly on December 14, 1992 from the complications of heart disease.
In his honor, The Oldendorf Award is given annually by the American Society of Neuroimaging based on the submission of a manuscript that involves clinical research in computerized tomography, magnetic resonance imaging, SPECT or PET scanning.