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at 3.6 ppm and MRS helps with diagnosis. Intermediate or long TE MRS is necessary to delineate glycine
from the myoinositol peak which overlap on a short TE spectrum.

ORNITHINE TRANCARBAMYLASE DEFICIENCY
Ornithine Transcarbamylase deficiency (OTCD) is the most common among the six enzyme deficiencies
in urea cycle disorders (UCD). OTC is a proximal enzyme of the urea cycle which is involved in the
conversion of ammonia to urea. Ammonia is a highly neurotoxic moiety. Hyperammonemia (HA)
can cause behavior changes, seizures and coma. One of the earliest changes on MRI is seen on MRS.
A glutamine peak is observed due to elevation during acute HA, with a corresponding myoinositol
reduction, presumably reflecting osmotic buffering [67-69] . OTCD disease severity correlates with glutamine
[11]
and inversely correlates with myoinositol concentrations . Reduction in choline occurs in patients with
recurrent decompensation and longstanding HA.

PET IMAGING
Positron emission tomography (PET) uses radioactive substances (tracers) to visualize and measure various
metabolic processes in the body. PET is mainly used to measure metabolism, blood flow, regional chemical
[70]
composition, and absorption .
FABRY DISEASE
Fabry disease (FD) is an X-linked lysosomal storage disorder, characterized by decreased or absent
activity of the lysosomal enzyme alpha galactosidase A due to mutation of the alpha galactosidase A gene
at Xq22.1. Clinical symptoms as a result of this accumulation include renal and cardiac failure, painful
acroparaesthesias, angiokeratomas, hypohydrosis, corneal dystrophy, and stroke [71-77] . Strokes are seen
in 25% of males and 21% of manifesting female carriers. PET imaging has been applied to Fabry disease
to determine if it adds any sensitivity. In one study, MRI was deemed sufficient for monitoring and PET
[78]
scanning with fluorodeoxyglucose (FDG-PET) does not add any further specificity .

FDG-PET was used to measure regional glucose metabolic rate in patients with phenylketonuria (PKU)
patients before and 4 months after sapropterin therapy. The study was limited by a small sample size
(5 subjects) and none had responded to sapropterin therapy; defined as 30% decrease in blood Phe level.
In addition, gglucose metabolism also appeared depressed in the cerebellum and left parietal cortex while
elevated in the frontal and anterior cingulate cortices as well as in left Broca’s area and right superior lateral
temporal cortex bilaterally .
[79]

FUNCTIONAL MRI
Roy and Sherrington first described neurovascular coupling in 1890 which forms the basis of MRI
[80]
findings. Sherrington’s work showed that neuronal metabolism and cerebral blood flow are linked and this
property is exploited to generate a blood oxygenation level-dependent (BOLD) signal in activated regions
of the brain. These are then used to generate an activation map for each task the participant performs
in the scanner. Active neurons consume glucose and oxygen, and this is restored by the local dilation of
cerebral vessels with increase in oxygenated hemoglobin. This occurs during an energy demanding process:
neurotransmission. The MRI pulse sequences are sensitive to the magnetic contrast between oxygenated
and deoxygenated hemoglobin and that gives rise to the signal on the MRI. As a result, it can be used to
map the hemodynamic response of local brain regions in relation to a cognitive, motor or resting state
[81]
activity .
After the study is completed, an activation map for a given task condition (working memory task, motor
task, resting state, etc.) can be constructed. Analysis in fMRI involves averaging scores across multiple